National Academy of Sciences
References
21. Res Commun Chem Pathol
Pharmacol 1992 Feb;75(2):251-4
Antioxidants and UV-induced genotoxicity.
Dreosti I, McGown M
Division of Human Nutrition, CSIRO (Australia),
Adelaide.
Genetic damage in mouse splenocytes exposed to UVA and UVB
irradiation in vitro
was demonstrated to be expressed as micronuclei in cell
cultures stimulated to
divide and blocked at cytokinesis. Because of the
involvement of active forms of
oxygen in UV-related genotoxicity, the present study
investigated the
photoprotective effect with respect to micronuclei, of the
antioxidant couple
vitamin C/E administered to mice in vivo or to cell cultures
in vitro prior to
UV irradiation of splenocytes in vitro. Significant
protection was observed in
both studies by antioxidant pretreatment, which highlights
the importance of
active oxygen in UV-induced genetic damage and suggests a
significant role for
nutritional antioxidants in sun damage prophylaxis.
22. Am J Surg 1991
Oct;162(4):294-8
Effects of N-acetyl-L-cysteine and ascorbic acid on
mutagen-induced chromosomal
sensitivity in patients with head and neck cancers.
Trizna Z, Schantz SP, Hsu TC
Department of Head and Neck Surgery, University of Texas M.
D. AndersonCancer
Center, Houston.
The protective effect of N-acetyl-L-cysteine (NAC) and
ascorbic acid on
mutagen-induced chromosomal breakage was determined using
human lymphoblastoid
cell lines as well as freshly cultured lymphocytes from
patients with head and
neck malignancies and healthy control subjects. Mutagen
sensitivity was
determined using the previously described bleomycin exposure
assay. The
toxicities of different concentrations of NAC and ascorbic
acid, as well as both
the preincubation and dose-dependent protective effects of
these two agents,
were analyzed. Both test drugs proved to be effective in
diminishing
mutagen-induced chromatid breakage in established lymphocyte
cell lines. In
freshly cultured lymphocytes, NAC given in doses ranging
from 0.1 to 10 mmol/L
decreased the number of mutagen-induced breaks per cell in a
range from 23% to
73%, and ascorbic acid decreased chromosomal breakage by 21%
to 58% in a dose
range from 0.01 to 1 mmol/L. The results of this study
demonstrate the
protective effect mediated in vitro by both NAC and ascorbic
acid against
mutagen-induced chromosomal damage. A similar in vivo
phenomenon may explain the
differences in occurrence of head and neck cancer between
populations with
different dietary backgrounds.
23. Mutat Res 1989
Oct;224(2):247-52
Vitamin C intake influences the bleomycin-induced chromosome
damage assay:
implications for detection of cancer susceptibility and
chromosome breakage
syndromes.
Pohl H, Reidy JA
Genetics Branch, Centers for Disease Control, Atlanta, GA
30333.
Supplementation with 1 g of vitamin C (ascorbic acid) per
day decreased the
amount of chromosome damage induced in lymphocytes by an
exposure to bleomycin
during the last 5 h of cell culture. We did not see such
changes in lymphocytes
from control individuals samples at the same time but not
taking vitamin C
supplements. This bleomycin assay has been proposed as a
test for cancer
susceptibility. A similar assay for genetic instability may
be useful in
detecting heterozygotes for chromosome-breakage syndromes
(for example, Fanconi
anemia or ataxia telangiectasia). Even though our sample
size is small and our
results should be interpreted cautiously, statistically
significant effects were
found with vitamin C supplementation. It would, therefore,
be prudent to
consider dietary and perhaps other lifestyle factors when
interpreting of
results from this bleomycin assay and related assays for
genetic instability.
24. Mutat Res 1989
Oct;224(2):247-52
Vitamin C intake influences the bleomycin-induced chromosome
damage assay:
implications for detection of cancer susceptibility and
chromosome breakage
syndromes.
Pohl H, Reidy JA
Genetics Branch, Centers for Disease Control, Atlanta, GA
30333.
Supplementation with 1 g of vitamin C (ascorbic acid) per
day decreased the
amount of chromosome damage induced in lymphocytes by an
exposure to bleomycin
during the last 5 h of cell culture. We did not see such
changes in lymphocytes
from control individuals samples at the same time but not
taking vitamin C
supplements. This bleomycin assay has been proposed as a
test for cancer
susceptibility. A similar assay for genetic instability may
be useful in
detecting heterozygotes for chromosome-breakage syndromes
(for example, Fanconi
anemia or ataxia telangiectasia). Even though our sample
size is small and our
results should be interpreted cautiously, statistically
significant effects were
found with vitamin C supplementation. It would, therefore,
be prudent to
consider dietary and perhaps other lifestyle factors when
interpreting of
results from this bleomycin assay and related assays for
genetic instability.
25. Mutat Res 1985
Mar;149(1):83-94
The action of anticlastogens in human lymphocyte cultures
and their modification
by rat-liver S9 mix. II. Studies with vitamins C and
E.
Gebhart E, Wagner H, Grziwok K, Behnsen H
The action of vitamins C (VC) and E (VE) on the
clastogenic activity of trenimon
(TR), cyclophosphamide (CP) and bleomycin (BM) was tested on
cultures of human
peripheral blood lymphocytes with and without addition of
rat-liver S9 mix. In
addition, the influence of both anticlastogens on the
SCE-inducing activity of
TR and CP was examined under the same conditions. A distinct
dose-dependent
anticlastogenic effect of VC was detected in the action of
long-term treatment
(24 h) with TR, if the vitamin was added to the cultures
simultaneously with or
before the clastogen. In the short-term tests (2 or 3 h
clastogen treatment
ending 23 h or 21 h before harvesting) simultaneous addition
of both vitamins
did reduce the chromosome-damaging action of TR whether S9
mix was present or
absent. While VC also decreased the frequency of chromosome
damage induced by
S9-mix-activated CP, VE was inactive under the same
conditions. Neither vitamin
significantly affected the chromosome-breaking activity of
BM if S9 mix was
absent, but they increased the clastogenicity of BM
metabolized by S9 mix. In
contrast to their anticlastogenic efficacy neither of the
vitamins displayed any
significant anti-SCE effect, nor were they active in
affecting the inhibition of
cell proliferation caused by TR or CP.
26. Mutat Res 1998 Nov
9;419(1-3):137-43
Effects of high doses of vitamins C and E against
doxorubicin-induced
chromosomal damage in Wistar rat bone marrow cells.
Antunes LM, Takahashi CS
Departamento Genetica, Faculdade Med. de Ribeirao Preto-USP,
Av. Bandeirantes,
3900, 14049-900, Ribeirao Preto, SP, Brazil.
lugreggi@fcfrp.usp.br
Doxorubicin (DXR) is one of the major antitumoral agents
available for clinical
use. In addition to intercalating into the DNA molecule,
this drug generates
free radicals. Vitamins C (VC) and E (VE) can protect normal
cells from the
damage caused by radicals without interfering with the
cytotoxicity of DXR
against tumors. The objective of the present study was to
investigate the
possible protective effect of VC and/or VE on mammalian
cells treated with DXR
in vivo. Animals treated with the lowest doses of VC and/or
VE, alone or in
combination, plus a single dose of DXR presented a
statistically significant
reduction in total number of chromosome aberrations and in
number of abnormal
metaphases. The highest vitamin doses tested caused no
changes in the parameters
analyzed when compared with control. Under the present
experimental conditions,
the efficiency of VC and/or VE in protecting against
chromosome damage was
dependent on the dose used. Copyright 1998 Elsevier Science
B.V.
27. Teratog Carcinog Mutagen
1998;18(4):153-61
Protective effects of the amino acid glutamine and of
ascorbic acid against
chromosomal damage induced by doxorubicin in mammalian
cells.
Tavares DC, Cecchi AO, Antunes LM, Takahashi CS
Departamento de Genetica, Faculdade de Medicina de Ribeirao
Preto, Universidade
de Sao Paulo, Brasil. dtavares@spider.usp.br
The interaction of antioxidants can provide an essential
protection against the
damaging effects of free radicals. Beneficial interactions
include
radioprotection, protection against acute toxicity of
chemicals, and
antimutagenic and anticarcinogenic activity. The present
study was undertaken to
evaluate the protective effect of the amino acid glutamine
(GLN) and ascorbic
acid (AA) on the frequency of chromosomal aberrations
induced by the
antineoplastic agent doxorubicin (DXR). These micronutrients
were tested
separately and simultaneously in Wistar rat bone marrow and
Chinese hamster
ovary (CHO) cells. The treatments with GLN and/or AA
significantly decreased the
frequency of DXR-induced clastogenic damage in both test
systems.
28. Carcinogenesis 1997
Jan;18(1):223-8
Ascorbic acid and beta-carotene as modulators of oxidative
damage.
Cozzi R, Ricordy R, Aglitti T, Gatta V, Perticone P, De
Salvia R
Dipartimento di Biologia, Universita degli Studi Roma Tre,
Italy.
Naturally occurring antioxidants are extensively studied
for their capacity to
protect organisms and cells from damage induced by oxygen
reactive species. In
fact, oxidative stress is considered a cause of aging,
degenerative disease and
cancer. We have focused our attention on two agents,
ascorbic acid and
beta-carotene, commonly considered to be antioxidants, but
whose protective
activity against cancer is insufficiently known. This paper
reports on the
ability of these agents to act against damage induced by
H2O2 and bleomycin, in
Chinese hamster ovary cells cultivated in vitro. Cytogenetic
and
cytofluorimetric analyses were performed. Both vitamins
proved effective in
reducing H2O2-induced sister chromatid exchanges, but
increased H2O2- and
bleomycin-induced chromosomal aberrations. Cytofluorimetric
data, in contrast,
showed that ascorbic acid and beta-carotene act as
scavengers of endogeneous and
H2O2-induced oxygen species.
29. Radiats Biol Radioecol 1995
Sep-Oct;35(5):726-9
[The anticlastogenic effect of ascorbic acid in relation to
the damages induced
in human lymphocytes by the photomutagenic action of
8-methoxypsoralen and by
ammonium molybdate].
[Article in Russian]
Makedonov GP, Bobyleva LA, Chekova VV, Zasukhina GD
In experiments with cultured human lymphocytes
anticlastogenic effect of
ascorbic acid (AA) with respect to photomutagenic action of
8-methoxypsoralen
(8-MOP) and ammonium molibdenate (Mo) was studied. It was
found that AA
effectively protected from mutagenic action of Mo. Effective
protection of cells
from 8-MOP monoadducts and DNA interstrand links was also
observed.
30. Radiats Biol Radioecol 1995
Sep-Oct;35(5):726-9
[The anticlastogenic effect of ascorbic acid in relation to
the damages induced
in human lymphocytes by the photomutagenic action of
8-methoxypsoralen and by
ammonium molybdate].
[Article in Russian]
Makedonov GP, Bobyleva LA, Chekova VV, Zasukhina GD
In experiments with cultured human lymphocytes
anticlastogenic effect of
ascorbic acid (AA) with respect to photomutagenic action of
8-methoxypsoralen
(8-MOP) and ammonium molibdenate (Mo) was studied. It was
found that AA
effectively protected from mutagenic action of Mo. Effective
protection of cells
from 8-MOP monoadducts and DNA interstrand links was also
observed.