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Growth retardation in human cervical
dysplasia-derived cell lines by beta - carotene through
down-regulation of epidermal growth factor receptor.
Muto Y; Fujii J; Shidoji Y; Moriwaki H; Kawaguchi T; Noda
T
First Department of Internal Medicine, Gifu University School
of Medicine, Japan.
Am J Clin Nutr Dec 1995, 62 (6 Suppl)
p1535S-1540S
We used newly established cervical dysplasia -derived cell
lines to elucidate a molecular mechanism of the preventive
action of beta - carotene in cervical multi-step
carcinogenesis. Liposomal beta - carotene was added to the
culture medium for human cervical dysplasia cell lines,
CICCN-2 from cervical intraepithelial neoplasia grade I (CIN
I), CICCN-3 from CIN II, and CICCN-4 from CIN III, and human
cervical carcinoma-derived cell lines such as CICCN-6,
CICCN-18, and HeLa cells. beta - Carotene (10 mumol/L) induced
significant growth retardation in three cervical dysplasia
cell lines but not in three cervical carcinoma-derived cell
lines. Binding activities of epidermal growth factor (EGF) and
cellular amounts of either messenger RNA for EGF receptor gene
or EGF receptor protein were all highest in CICCN-4 cells.
Cell surface binding, as well as internalization, of
125I-labeled EGF was rapidly reduced after beta - carotene
treatment in dysplasia cell lines and 170-kD protein bands of
EGF receptor disappeared from protein immunoblots at day 3 of
the treatment. Cellular amounts of EGF receptor messenger RNA
remained constant until day 3 of the treatment and were
substantially reduced after day 7. Chromatin condensations,
morphologic evidence for apoptotic cell death, were observed
at day 1 by staining. From these results, we contend that
prevention of cervical carcinogenesis by beta - carotene is
due to induction of apoptosis in cervical dysplastic cells,
which are premalignant cells in cervical multi-step
carcinogenesis, via down-regulation of EGF receptor
protein.
Growth suppression and induction of heat-shock
protein-70 by 9-cis beta - carotene in cervical
dysplasia-derived cells.
Toba T; Shidoji Y; Fujii J; Moriwaki H; Muto Y; Suzuki T;
Ohishi N; Yagi K
First Department of Internal Medicine, Gifu University School
of Medicine, Japan.
Life Sci (England) 1997, 61 (8) p839-45
The aim of the present study was to determine to what
extent 9-cis beta- carotene , one of the most abundant
naturally-occurring cis-isomers of beta -carotene , can
inhibit the growth of cervical dysplasia -derived cells in
comparison with all-trans beta -carotene . We found that 9-cis
beta -carotene was dose-dependently more effective than
all-trans beta - carotene . Both carotenes induced the
intracellular accumulation of heat-shock protein-70 (HSP70),
and the treated cells showed morphological changes indicative
of apoptosis. The results of the present study strongly
suggest that the induction of HSP70 by beta -carotene might be
involved in beta - carotene -mediated suppression of the cell
growth through apoptosis.
Oral contraceptive use and adenocarcinoma of
cervix
Ursin G; Peters RK; Henderson BE; d'Ablaing G 3rd; Monroe KR;
Pike MC
Department of Preventive Medicine, University of Southern
California School of Medicine, Los Angeles 90033-9987.
Lancet (England) Nov 19 1994, 344 (8934) p1390-4
The incidence of adenocarcinoma of the cervix in the USA
more than doubled between the early 1970s and the mid 1980s
among women under 35 years of age. It was suggested that this
increase was due to the introduction of oral contraceptives in
the early 1960s. Adenocarcinoma of the cervix diagnosed in
women born after 1935 was identified between 1977 and 1991
from the Los Angeles County Cancer Surveillance Program. Data
from personal interviews of 195 cases and 386 controls
(matched on age, race, and neighbourhood) were analysed.
Information on medical, sexual, contraceptive, and
reproductive history, previous cervical smears, and sexually
transmitted diseases was collected. Compared with never use,
ever use of oral contraceptives was associated with twice as
great a risk of adenocarcinoma of the cervix (adjusted odds
ratio 2.1, 95% CI 1.1-3.8). The highest risk was observed for
oral contraceptive use for more than 12 years (4.4, 1.8-10.8).
No additional increased risk was found for early age at start
of oral contraceptive use, use before age 20 or before first
pregnancy, time since first use, time since last use, or
particular formulations, once total duration of use had been
accounted for.
Comparison of oral contraceptive use in women with
adenocarcinoma and squamous cell carcinoma of the uterine
cervix.
Honore LH; Koch M; Brown LB
Department of Pathology, University of Alberta, Edmonton,
Canada.
Gynecol Obstet Invest (Switzerland) 1991, 32 (2)
p98-101
The possible link between oral contraceptives (OCs) and
cervical adenocarcinoma was tested by a case-case study of
prior and current OC use in women with adenocarcinoma and
squamous cell carcinoma. Cases were matched by age, year of
diagnosis, and stage of the lesion, and personal,
reproductive, and contraceptive data were obtained by mailed
questionnaires. Except for smoking, which was significantly
more prevalent in women with squamous cell carcinoma, the two
groups were identical, with similar OC exposure. This study
does not support the idea that OCs modulate the expression of
cervical neoplasia in favor of adenocarcinoma.
Oral contraceptive use and invasive cervical
cancer.
Parazzini F; la Vecchia C; Negri E; Maggi R
Mario Negri Institute for Pharmacological Research, Milan,
Italy.
Int J Epidemiol (England) Jun 1990, 19 (2)
p259-63
The relationship between oral contraceptive use and the
risk of invasive cervical cancer was investigated using data
from a hospital-based case-control study conducted in the
greater Milan area, Northern Italy. A total of 367 women under
60 years of age with a histologically confirmed diagnosis of
invasive cervical cancer was compared with a group of 323
controls admitted for a spectrum of acute conditions,
non-gynaecological, hormonal or neoplastic and apparently
unrelated to oral contraceptive use . Cases had used oral
contraceptives more frequently than controls, the age-adjusted
relative risk (RR) being 1.53 (95% confidence interval
0.99-2.36). The risk increased with duration of use: compared
with never users the age-adjusted RR was 1.48 for up to two
years and 1.83 for more than two years (chi 2(1) = 5.28, p =
0.02). Allowing for major identified potential confounding
factors, including sexual and reproductive habits, by means of
multiple logistic regression, did not explain the association
(multivariate RR 1.85 for ever use, 1.05 for up to two years
and 2.47 for more than two years). When the interaction
between oral contraceptive use and parity or sexual habits was
analysed, the effects of various factors appeared independent:
the point estimate for multiparous oral contraceptive users
versus nulliparous never users was 8.01. There was no
consistent influence on risk of invasive cervical cancer of
age at first use, whereas the RRs were slightly greater for
women who had first used oral contraceptives less than ten
years before or had last used them less than five years before
diagnosis: these findings, however, were far from
significant.
Oral contraceptive use and risk of invasive
cervical cancer.
Brinton LA; Reeves WC; Brenes MM; Herrero R; de Britton RC;
Gaitan E; Tenorio F; Garcia M; Rawls WE
Environmental Epidemiology Branch, National Cancer Institute,
Bethesda, MD 20892.
Int J Epidemiol (England) Mar 1990, 19 (1) p4-11
A case-control study of 759 invasive cervical cancer
patients and 1430 controls in Panama, Costa Rica, Colombia and
Mexico enabled an evaluation of risk in relation to oral
contraceptive use . Overall use was associated with a 21%
nonsignificant elevation in risk, with some further increases
in risk for more extensive durations of use. Although risks
were similar for recent and non-recent users (RRs = 1.3 versus
1.2), recent long-term users were at highest risk (RR for 5+
years use = 1.7, 95% Cl 1.1-2.6). Relationships were similar
for women with and without a recent Pap smear, arguing against
detection bias. There was little evidence that other risk
factors, including smoking and detection of human
papillomaviruses (HPV), altered the effects of oral
contraceptives. The risk associated with oral contraceptives
was significantly increased for adenocarcinomas (RR = 2.2),
whereas for squamous cell tumours the effect was minimal (RR =
1.1). These results provide some support for an adverse effect
of oral contraceptives on cervical cancer risk, although
possibly limited only to a subpopulation of cases.
Use of oral contraceptives and risk of invasive
cervical cancer in previously screened women.
Ebeling K; Nischan P; Schindler C
Int J Cancer (United States) Apr 15 1987, 39 (4)
p427-30
Within the context of a larger hospital-based case-control
study carried out to assess the efficacy of cervical cancer
screening, the possible association between oral
contraceptives and risk of invasive cervical cancer has been
studied as well. Because in the GDR cytological screening is
an integral part of the gynaecological basic care, only a few
women reported oral contraceptive use but had no Pap-smears in
that study. Thus, the analysis was confined to those 129 cases
and 275 controls who had at least one screening Pap-smear in
their history and were below the age 55. The significantly
increased relative risks for users decreased after adjustment
for factors of sexual behaviour and interval since last
Pap-smear but remained statistically significant or at
borderline significance for some categories of usage. This
concerns, in particular, long-term use (7+ years) and early
onset of use (less than or equal to 24 years) with relative
risks of 1.8 and 3.0, respectively.
Long-term use of oral contraceptives and cervical
neoplasia: an association confounded by other risk
factors?
Hellberg D; Valentin J; Nilsson S
Contraception Oct 1985, 32 (4) p337-46
One-hundred-and-forty women with cervical intraepithelial
neoplasia (CIN) found during pregnancy were compared to 280
pregnant age-matched controls. Information was obtained on
obstetrical and gynecological history, sexual behaviour,
contraceptive use and smoking of the female and of the male
partner. Oral contraceptive use for 60 months or more was
significantly associated with CIN. This significance vanished
when the effect of confounding factors was controlled for in a
log-linear analysis. According to these results, long-term
oral contraceptive use does not seem to be a causal factor of
CIN, but these women constitute a high risk group due to
sexual history and smoking habits and should thus be referred
for a regular cytological screening.
Oral contraceptives and cervical neoplasia
Brinton L.A.
Environmental Epidemiology Branch, National Cancer Institute,
Executive Plaza North, Bethesda, MD 20892 United States
Contraception 1991, 43/6 (581-595)
Although initial studies examining the relationship of oral
contraceptives to risk of cervical neoplasia were reassuring,
more recent studies provide some evidence of a positive
relationship, particularly for long-term usage. Results,
however, are difficult to interpret, because of a variety of
methodologic complexities, including potential sources of
confounding and bias. Sexual behavior and Pap smear screening
have been identified as important confounders, but in several
well-controlled studies residual excess risks of nearly 2-fold
persist for users of 5 or more years. A possible promotional
effect of oral contraceptives is suggested by higher risks
associated with recent usage. There also is some suggestion of
a stronger effect for adenocarcinomas than for squamous cell
tumors. A relationship is biologically possible, given
findings of hormone receptors in cervical tissue and the fact
that oral contraceptives have been found to induce cervical
hyperplasia. In addition, oral contraceptives may induce
proliferation of the human papillomaviruses, the leading
suspect agent for cervical cancer. Although a number of lines
of evidence support a relationship of oral contraceptives to
cervical cancer risk, firm conclusions await the results of
additional studies that specifically address some of the
methodologic shortcomings of previous investigations. In
particular, additional follow-up studies are needed to define
the effect of oral contraceptives on the natural history of
cervical lesions.
Case-control study of risk factors for cervical
squamous- cell neoplasia in Denmark. III. Role of oral
contraceptive use.
Kjaer SK; Engholm G; Dahl C; Bock JE; Lynge E; Jensen
OM
Danish Cancer Society, Copenhagen.
Cancer Causes Control (England) Nov 1993, 4 (6)
p513-9
The role of oral contraceptive (OC) use in relation to the
risk of cervical neoplasia (squamous cell) was investigated in
a population-based case-control study in Denmark of 586 women
with histologically verified cervical carcinoma in situ (CIS),
59 women with invasive cervical cancer from Copenhagen, and
614 controls drawn at random from the female population in the
study area. Ever use of OCs was associated with an increased
crude risk for carcinoma in situ (relative risk [RR] = 1.8, 95
percent confidence interval [CI] = 1.3-2.5). The crude risk in
relation to invasive carcinoma was 1.6 (CI = 0.7-3.5). After
adjustment for potential confounders (excluding human
papillomavirus), the risks were marginally increased, but not
statistically significant (CIS: RR = 1.4, CI = 0.9-21:
invasive: RR = 1.3, CI = 0.5-3.3). The risk increased with
duration of use; compared with never users, the adjusted RR
for carcinoma in situ was 1.9 (CI = 1.1-3.1) for women who had
used OCs for six to nine years, and 1.7 (CI = 1.0-2.7) for
women who used OCs for 10 years or more. This was independent
of years since last use since both recent and non-recent
long-term users were at an increased risk. This trend in risk
with duration did not apply to the same extent to invasive
lesions. The observation that the risks related to OC use were
found both in women who had ever had a Pap smear and in women
who had never been screened previously may speak against
detection bias as an important factor.
Oral contraceptive use and cervical intraepithelial
neoplasia.
Coker AL; McCann MF; Hulka BS; Walton LA
Department of Epidemiology and Biostatistics, University of
South Carolina, Columbia 29208.
J Clin Epidemiol (England) Oct 1992, 45 (10)
p1111-8
To explore the somewhat controversial relationship between
oral contraceptives and pre-invasive cervical cancer, 103
cases of biopsy-confirmed cervical intraepithelial neoplasia
(CIN) II or CIN III were compared with 258 controls who had
normal cervical cytology. Cases were slightly less likely than
controls to have ever used oral contraceptives; the odds
ratio, controlling for age, socioeconomic status, barrier
method use, smoking history, age at first sexual intercourse,
number of sex partners, current marital status, and number of
Pap smears, was 0.7 (95% CI 0.3-1.6). Recency, latency,
duration, and age at first oral contraceptive use were
evaluated and in no instance was oral contraceptive use
positively associated with CIN. This study adds to the body of
knowledge that oral contraceptives are not associated with
pre-invasive cervical cancer. Further, if oral contraceptive
users continue to be regularly screened, their risk of
developing the more invasive lesions should be very low.
Oral contraceptive use and the incidence of
cervical intraepithelial neoplasia
Gram IT; Macaluso M; Stalsberg H
Institute of Community Medicine, University of Tromso,
Norway.
Am J Obstet Gynecol Jul 1992, 167 (1) p40-4
OBJECTIVE: Our objective was to examine the relationship
between oral contraceptive use and the incidence of cervical
intraepithelial neoplasia.
STUDY DESIGN: In a prospective follow-up study of 6622
women participating in the Second Tromso Study conducted in
1979 and 1980 in Tromso, Norway, women aged 20 to 49 years
answered a questionnaire regarding their smoking history,
dietary habits, alcohol consumption, and oral contraceptive
use . They were then followed for 10 years with data from the
Pathology Registry of the University Hospital.
RESULTS: The age-adjusted incidence rate of cervical
intraepithelial neoplasia was 897 per 100,000 person years
among noncurrent and 1295 per 100,000 person years among
current oral contraceptive users as of 1979. After adjusting
for age, marital status, smoking, and frequency of alcohol
intoxication the relative rate for current users was 1.5 (95%
confidence interval 1.1 to 2.1), and the relative rate for
past users was 1.4 (95% confidence interval 1.0 to 1.8), as
compared with those who had never used oral contraceptives
before 1979.
CONCLUSION: These findings support the hypothesis that the
occurrence of cervical intraepithelial neoplasia is increased
by oral contraceptive use .
A case-control study of oral contraceptive use in
women with adenocarcinoma of the uterine cervix.
Persson E; Einhorn N; Pettersson F
Department of Obstetrics and Gynecology, Karolinska Hospital,
Stockholm, Sweden.
Eur J Obstet Gynecol Reprod Biol (Netherlands) Sep 1987, 26
(1) p85-90
To evaluate oral contraceptive (OC) use as a possible cause
of the changed ratio between adenocarcinoma and squamous cell
carcinoma of the uterine cervix a case-control study was
performed. The OC use among 23 women with adenocarcinoma of
the uterine cervix was compared with that of a matched group
of 46 women with squamous cell carcinoma. No differences in
percentage of OC use, duration of such use or period of OC use
in relation to diagnosis could be demonstrated between the two
groups compared.
A longitudinal analysis of human papillomavirus 16
infection, nutritional status, and cervical dysplasia
progression.
Liu T; Soong SJ; Alvarez RD; Butterworth CE Jr
Biostatistics Unit, University of Alabama at Birmingham
35294-3300, USA.
Cancer Epidemiol Biomarkers Prev Jun 1995, 4 (4)
p373-80
To evaluate the effect of potential risk factors,
especially human papillomavirus type 16 (HPV-16) infection and
nutritional status on the course of cervical dysplasia , we
analyzed data from an intervention trial conducted from 1985
to 1990, in Birmingham, Alabama. With the use of data of four
repeated evaluations of dysplasia at an interval of 2 months,
specific relationships between HPV-16 infection, plasma
retinol and zinc levels, and dysplasia progression were
evaluated through longitudinal data analysis of generalized
estimating equations. Repeated assessments of nutritional
status from blood samples, HPV-16 infection, and dysplasia
diagnosis were available from 206 women. Dysplasia diagnosis
was confirmed by both Papanicolaou smear and colposcopy
examinations and was classified as normal, low, or high grade
squamous intraepithelial lesions according to the Bethesda
system and assigned a score of 0, 1, or 2, respectively.
Generalized estimating equation analyses were performed with
assumptions of variance of Poisson and link of logarithm.
Separate analyses were also conducted for HPV-16-positive and
HPV-16-negative women. By multivariate modeling with
adjustment for age, race, smoking, oral contraceptive use, and
plasma levels of nutrients, HPV-16 infection was found to be
related to the progression of cervical dysplasia , with a
relative risk of 1.19 and a 95% confidence interval of
1.03-1.38. High plasma levels of retinol were related to the
regression of cervical dysplasia , especially in
HPV-16-positive women. A protective effect was also observed
for high levels of zinc.(ABSTRACT TRUNCATED AT 250 WORDS)
Zinc concentration in plasma and erythrocytes of
subjects receiving folic acid supplementation
Butterworth Jr. C.E.; Hatch K.; Cole P.; Sauberlich H.E.;
Tamura T.; Cornwell P.E.; Soong S.-J.
Department of Nutrition Sciences, University of Alabama at
Birmingham, Birmingham, AL 35294 United States
American Journal of Clinical Nutrition 1988, 47/3
(484-486)
It has been suggested that oral supplements of folic acid
interfere with the intestinal absorption of zinc and may have
toxic side effects. The concentrations of Zn and folate in
blood were monitored in a group of women with cervical
dysplasia randomly assigned to receive 10 mg/d of either folic
acid (pteroylglutamic acid) or ascorbate. Fifty subjects were
evaluated after 2 mo; 21 of the same subjects were evaluated
again after 4 mo. No untoward clinical effects were observed.
Significant elevation of erythrocyte folate above the baseline
value was observed in the supplemented group but not in the
placebo group (p < 0.001). The concentration of Zn in
plasma and erythrocytes did not change significantly in either
the folate -treated or placebo groups after 2 and 4 mo. It is
concluded that carefully controlled clinical intervention
trials of this type do not impose a risk of depleting the
concentration of Zn in erythrocytes and plasma.
Stress and hopelessness in the promotion of
cervical intraepithelial neoplasia to invasive squamous cell
carcinoma of the cervix
Goodkin K; Antoni MH; Blaney PH
J Psychosom Res (England) 1986, 30 (1) p67-76
[published erratum appears in J Psychosom Res
1987;31(5):659]
Stress and hopelessness have been associated with the
development of invasive cervical cancer by previous research.
Subjects in this study were recruited from a colposcopy clinic
awaiting work-up of an abnormal pap smear and from those
admitted to an in-patient gynecology ward for cone biopsy of
the cervix or hysterectomy to treat a symptomatic pelvic mass
thought to be uterine leiomyomas. After data collection,
pathology reports and colposcopic findings were used to
determine group assignment independent of subjects' knowledge
of their diagnosis. A modest stress - promotion correlation
was derived, which was greatly enhanced by significant
interactions with low levels of cooperative coping style and
for high levels of premorbid pessimism, future despair,
somatic anxiety, and life threat reactivity. These stress
-moderator interactions are discussed in terms of immune
system deficit with concomitant enhancement of promotion of
CIN to invasive squamous cell cervical cancer.
[Relation between selenium and cancer of uterine
cervix]
Lou H; Wu R; Fu Y
Zhejiang Cancer Hospital, Hangzhou.
Chung Hua Chung Liu Tsa Chih (China) Mar 1995, 17 (2)
p112-4,
Selenium (Se) concentration in serum, hair, normal cervix
tissue ortissue of cervix cancer of 20 cases with cancer of
uterine cervix (surveygroup), 21 with myoma of the uterus and
1 with cervical polys (control group), but also in rice, water
and soil in the high and low incidence areas of cervical
cancer was determined. The results showed that Se
concentration in serum and cancer tissue of uterine cervix in
patients with cancer of uterine cervix was significantly lower
than that in the control group (P < 0.05), but no
significant difference of Se concentration in hair was
observed (P > 0.05), However Se concentration in rice,
water and soil in the high incidence areas of cervical cancer
was significantly lower than that in the low incidence areas
(P < 0.05). Se deficiency may play a role in the
carcinogenesis of uterine cervix.
Serum selenium and the risk of cancer, by specific
sites: case-controlanalysis of prospective data.
Nomura A; Heilbrun LK; Morris JS; Stemmermann GN
J Natl Cancer Inst Jul 1987, 79 (1) p103-8
From 1971 to 1975, serum specimens were obtained from 6,860
men ofJapanese ancestry in Hawaii. Since then, the following
numbers of newly diagnosed cases with epithelial cancer have
been identified: 82 colon, 71 lung, 66 stomach, 32 rectum, and
29 urinary bladder. The stored sera of the 280 cases and of
293 randomly selected controls were tested to determine their
levels of selenium. There was no association of serum selenium
with lung, stomach, or rectal cancer. An increase in relative
risk (RR) was noted only for subjects in the lowest quintile
of selenium values, as compared to the RR for subjects in the
highest quintile, for colon (RR = 1.8) and urinary bladder
cancer (RR = 3.1), but neither of these RR estimates was
statistically significant (P = .09 and P = .07, respectively).
Further work is needed to determine whether the antioxidant
properties of selenium protect against specific types of
cancer.
Chemopreventive action of selenium on
methylcholanthrene-inducedcarcinogenesis in the uterine cervix
of mouse.
Hussain SP; Rao AR
Cancer Biology Laboratory, School of Life Sciences,
Jawaharlal Nehru University, New Delhi, India.
Oncology 1992, 49 (3) p237-40
The placement of cotton thread impregnated with beeswax
containingmethylcholanthrene (MCA, approximately 600
micrograms) inside the canal of the uterine cervix of virgin,
adult mice results in the emergence of precancerous and
cancerous lesions in the cervical epithelium. Employing this
experimental carcinogenesis model system, the present study
evaluates the chemopreventive action of selenium on the
incidences of precancerous and cancerous lesions in the
cervical epithelium. When selenium was administered through
drinking water at the dose level of 1 ppm for 1 week before
and 12 weeks following carcinogen thread insertion, the
cervical carcinoma incidence, as compared to that in control
mice (72%), was 37%. This decline in the incidence of
carcinoma was significant (p less than 0.05). The incidences
of hyperplasia and dysplasia show a decreasing trend with
selenium treatment in MCA-thread-inserted animals.
Dietary vitamins A, C, and E and selenium as risk
factors for cervicalcancer.
Slattery ML; Abbott TM; Overall JC Jr; Robison LM; French TK;
Jolles C; Gardner JW; West DW
Department of Family and Preventive Medicine, University of
Utah School of Medicine, Salt Lake City 84132.
Epidemiology Jan 1990, 1 (1) p8-15
The relation between cervical cancer and dietary intake of
vitamins A, C,and E, beta-carotene, and selenium was examined
in a population-based case-control study in Utah. Cervical
cancer cases (n = 266) and population-based controls (n = 408)
were interviewed between 1984 and 1987. Protective effects
were observed for vitamins A, C, and E and beta-carotene but
were attenuated by age, level of education, and lifetime
cigarette use. Associated risk (comparing highest with lowest
quartiles of intake) went from 0.53 (crude) to 0.71 (adjusted)
for vitamin A; from 0.55 (crude) to 0.82 (adjusted) for
beta-carotene; from 0.45 (crude) to 0.55 (adjusted) for
vitamin C; from 0.58 (crude) to 0.60 (adjusted) for vitamin E;
and from 0.95 (crude) to 0.70 (adjusted) for selenium.
Adjustment for number of sex partners and church attendance,
factors significantly related to cervical cancer risk, only
slightly attenuated these adjusted risk estimates.
[Concentration of selenium and vitamin E in the
serum of women withmalignant genital neoplasms and their
family members]
Drozdz M; Tomala J; Jendryczko A; Banas K
Ginekol Pol (Poland) Jun 1989,60 (6) p301-5
Lower concentrations of selenium and vitamin E were found
in the serum of 50 women with malignant neoplasms of the
genitals as compared with the concentrations in 55 healthy
women family members of the patients living with them in
common households. The degree of concentration decrease of
these substances in the serum depended on the location of the
tumour, and in cases of cervical neoplasms was 28% for
selenium and 12% for vitamin E of the values in controls while
in cases of ovarian neoplasms it was 34% and 37% respectively
and in endometrial tumours it was 40% and 23% respectively.
The third studied group comprised 36 healthy subjects not
belonging to the families of the patients. The highest
concentrations of selenium and vitamin E were found in the
serum in the third group of women. The results suggest that
various family factors not analysed in this study affect the
concentrations of selenium and vitamin E in the serum of women
with malignant neoplasms of genitals and in their family
members.
Relationship between the cervical uterine cancer
evolution and selenium concentration in urine determined by
NAA
Navarrete M.; Cabrera L.; Martinez T.; Revel G.; Meyer J.P.;
Guarner J. M. Navarrete,
National University of Mexico, Faculty of Chemistry, Bldg.
D., C.U. 04510 Mexico City Mexico
Journal of Radioanalytical and Nuclear Chemistry (Hungary)
1997, 217/2 (167-169)
Neutron activation analysis of Se in urine roaches an
optimum sensitivity few ppb) and precision (+/- 12%) when the
traces are complexed without using a carder by ammonium
pyrrolidindithiocarbamate (APDC) at pH 1.5-2 and adsorbed on
activated carbon filters. In this way the selenium traces
analysis have been carded out through sup 7sup 7sup mSe in 45
urine samples on a pre-separation basis by cyclic activation
of the carbon filters. The selenium concentration in our
blanks is virtually zero, because APDC proved to be selenium
free and selenium mass in 50 mg of activated carbon used as a
filter is 20 times below our qualitative detection limit and
144 times below our quantitative detection limit. The samples
were first of day urine from healthy and ill women suffering
cervical uterine cancer, at different evolution stages:
incipient, intermediate and advanced, with no treatment, and
surgery, radiotherapy, chemotherapy, or a combined treatment.
The results show a consistent trend to increase the selenium
trace concentration during the intermediate stage, whereas it
is the same than normal for incipient cases, and it decreases
to the lowest concentrations for advanced cases.
Activation analysis of selenium in cancer
research
Navarrete M.; Cabrera L.; Martinez T.; Revel G.; Meyer J.P.;
Stampfler A.
National University of Mexico, Faculty of Chemistry,04510
Mexico City Mexico
Journal of Radioanalytical and Nuclear Chemistry (Hungary)
1995, 195/1 (91-95)
The method described in a previous work to separate trace
amounts of selenium in organic samples without using a
carrier, based on the adsorption on active carbon filters of
the complex formed with ammonium pyrrolidindithiocarbamate
(APDC) at pH 1.5-2, has been applied to urine samples from 15
female patients suffering from cervical uterine cancer. With
this type of sample the method reaches a maximum sensitivity
(few ppb) with a good statistical variation (+/- 12%). Since
the highest concentrations of selenium in human tissues is
found in the kidney, and the elimination of this element is
mainly by the urine, the method seems to be a powerful tool in
the research about the human metabolism of selenium. This
paper shows a possible relation of selenium concentration in
human urine and the evolution time of cervical uterine cancer,
in spite of limits imposed by the statistical error plus the
inhomogeneity of the sample.
Low serum selenium concentration in patients with
cervical or endometrialcancer.
Sundstrom H; Yrjanheikki E; Kauppila A
Int J Gynaecol Obstet (Ireland) Feb 1984, 22 (1)
p35-40
Serum concentrations of selenium were determined in 37
patients with cervical and 64 patients with endometrial
cancer. The patients had lower (P less than 0.001) serum
concentrations of selenium than the age-, weight-and place of
residence-matched paired control women. There was no
difference in the selenium concentration between various age
groups or different clinical stages of cervical or endometrial
cancer. A low serum concentration of selenium might be a
contributing factor in uterine carcinogenesis.
Pyridoxine, the pill and depression Adams
P.W.Alexander Simpson
Lab. Metab. Res., St Mary's Hosp. Med. Sch., London W2
United Kingdom Journal of Pharmacotherapy (United Kingdom)
1980, 3/1 (20-29)
Depression is associated with altered metabolism of brain
amines which are derived from tryptophan and tyrosine, the
metabolism of which is also deranged by oral contraceptives
(OC). The effects of OC on tryptophan metabolism are mediated
by induction of the rate-limiting enzyme of its major
catabolic pathway, and impaired pyridoxal phosphate (derived
from vitamin B6)-dependent co-enzyme function. The majority of
women on OC have functional B6 deficiency, but a small
proportion have vitamin B6 deficiency with evidence of lowered
tissue levels of this vitamin. As the dose of pyridoxine
recommended for the treatment of depression of women on OC is
excessive and may have metabolic side-effects, the minimum
dose of pyridoxine has to be established that will correct the
symptoms and metabolic abnormalities in women with OC-induced
deficiency of vitamin B6.
Physiological and psychological effects of vitamins
E and B-6 on women taking oral contraceptives
Applegate W V; Forsythe A; Bauernfeind J B
South. Calif. Perm. Med. Group, 8010 Parkway Dr., La Mesa,
Calif. 92041, USA.
Int J Vitam Nutr Res 49 (1). 1979. 43-50.
A substantial number of women on oral contraceptives have
low blood levels of vitamin E. When d,l .alpha.-tocopheryl
1200 IU is administered daily for 3-4 mo., there is
improvement of hematocrit for those attaining a serum level
greater than 11 mcg/ml and serum vitamin E level is
significantly elevated. Platelet count is depressed into the
low normal range so caution should be exercised in
administering vitamin E in high doses to patients already on
medication such as aspirin or thiazides that may further
depress platelet function or count. No toxicity or side
effects from using high doses of vitamin E could be discerned.
Vitamin B6 almost completely nullified the effect of vitamin E
on hematocrit, platelet count and serum vitamin E when
administered concurrently. Vitamin B6 30 mg/day also
significantly elevated mood in 56% of the women who received
it. The diet of women on oral contraceptives should be
supplemented with vitamin E and vitamin B6 (administered at
separate times). The importance of supplementing vitamin B6
becomes even more urgent when one considers that urinary
metabolites resulting from the abnormal breakdown of
tryptophan in the presence of vitamin B6 deficiency are
implicated in the production of cancer of the urinary bladder.
The depressing of platelet count by high doses of of vitamin E
in women taking oral contraceptives can be considered
beneficial as these women are predisposed to deep vein
thrombosis.
Influence of oral contraceptives, pyridoxine
(vitamin B6), and tryptophanon carbohydrate metabolism.
Adams PW; Wynn V; Folkard J; Seed M
Lancet (England) Apr 10 1976, 1 (7963) p759-64
Carbohydrate metabolism and vitamin-B6 status were assessed
before andafter pyridoxine administration in 46 women taking
combinedoestrogen-progestagen oral contraceptives (O.C.). 18
women had evidence of tissue depletion of vitamin B6, although
all the women had abnormal tryptophan metabolism, including
increased urinary xanthurenic acid (X.A.) excretion. In the
women with vitamin B6 deficiency, administration of this
vitamin caused elevation of fasting blood-pyruvate levels, and
reduction in plasma glucose, insulin, and blood-pyruvate
responses after an oral glucose load. These changes in
carbohydrate metabolism were not found in the 28
non-vitamin-B6-deficient women. These results indicate that
carbohydrate intolerance in women on O.C. is unlikely to be
mediated by the formation of a complex of X.A. with insulin,
as has formerly been proposed. Since the synthesis of the
tryptophan metabolite quinolinic acid, an inhibitor of the
heptaic enzyme phosphoenolpyruvate carboxykinase, may be
enhanced by the administration of pyridoxine, it is suggested
that this metabolite might be the important factor in the
improvement of glucose tolerance in the vitamin-B6-deficient
women. This conclusion is supported by the improvement in
glucose tolerance observed in 6 women on O.C. and in 4
patients with glucocorticoid excess who were not vitamin-B6
deficient, when they were given tryptophan to augment the
synthesis of quinolinic acid.
Does use of oral contraceptives enhance the
toxicity of carbon disulfidethrough interactions with
pyridoxine and tryptophan metabolism?
Calabrese EJ
Med Hypotheses (England) Jan 1980, 6 (1) p21-33
It is proposed that oral contraceptive (OC) users are at
increased risk to experiencing adverse psychological disorders
(e.g. irritability, depression) from exposures to elevated
levels of carbon disulfide (CS2). This theory is based on
studies indicating that both OCs and CS2 induce either a
vitamin B6 deficiency and/or enhance its requirement. Since
disruptions of B6 metabolism are thought to explain, at least
in part, the adverse psychological effects of OCs and CS2, it
is speculated that joint exposure to these substances may
result in an exaggerated disruption of B6 metabolism with the
development of CS2 induced adverse psychological effects
occurring at exposure levels below those normally associated
with adverse effects.
Drug--vitamin B6 interaction.
Bhagavan HN; Brin M
Curr Concepts Nutr 1983, 12 p1-12
In conclusion, there are several drug types that can
interfere withvitamin B6 metabolism. In most cases, the
interaction involves a complex formation between the drug (or
a derivative) and the reactive coenzyme PLP, resulting in a
Schiff base. Such an interaction leads to an inactivation of
PLP (and also of the drug). Other types of interaction involve
(a) stimulation of vitamin B6-dependent pathways and (b)
competition with PLP for the binding site on the enzyme.
Examples of the above are the steroid hormones (oral
contraceptives). In most instances, overt symptoms of vitamin
B6 deficiency due to chronic ingestion of these drugs are
observed, and neurological problems seem to be rather
frequent. Because of the reactive nature of the coenzyme PLP
and the ease with which it can interact with drugs,
sub-clinical (marginal) vitamin B6 deficiency should be
suspected in the absence of overt clinical signs. Once the
vitamin B6 problem has been identified, the condition can
usually be treated by judicious use of large doses of vitamin
B6 without compromising the clinical efficacy of the drug. (22
Refs.)
The effect of oral contraceptives on the apparent
vitamin B6 status insome Sudanese women.
Salih EY; Zein AA; Bayoumi RA
Faculty of Medicine, University of Khartoum, Sudan.
Br J Nutr (England) Sep 1986, 56 (2) p363-7
1. In vitro activation of erythrocyte aspartate
aminotransferase (EC2.6.1.1) activity by pyridoxal phosphate
was used to assess vitamin B6nutritional status in forty
Sudanese women taking combined, low-dose oralcontraceptives
(oestrogen-progestogen; OC) and in thirty healthy,
non-pregnant women not taking OC.
2. Fourteen (35%) out of forty OC users showed apparent
vitamin B6 deficiency.
3. Side-effects associated with OC were more common among
the apparently vitamin-B6-deficient OC users than among OC
users and non-OC users not deficient in vitamin B6.
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