A study of 748 cases and 1,411 hospital and community controls in four Latin
American countries evaluated the association between certain elements of diet
and invasive cervical cancer. Subjects were interviewed about their adult
consumption of 58 food items, including the major sources of putative protective
agents (vitamin A, carotenoids, vitamin C, and folacin) as well as other
behavioral and medical characteristics related to cervical cancer. Participation
rates were above 95% for both cases and controls. After adjustment for age,
study site, sexual and reproductive behavior, socioeconomic status, screening
practices, and detection of human papillomavirus 16/18 by filter in situ
hybridization, a slightly lower risk was observed for the highest quartiles of
consumption of fruit and fruit juices, while no reductions in risk were
associated with vegetables, foods of animal origin, complex carbohydrates,
legumes, or folacin-rich foods. When nutrient indices were derived, significant
trends of decreasing risk were observed for vitamin C (adjusted odds ratio (OR)
= 0.69 for the highest vs. the lowest quartile; p for trend = 0.003),
beta-carotene (OR = 0.68; p = 0.02), and other carotenoids (OR = 0.61; p =
0.003). Inclusion of vitamin C and beta-carotene in the same model attenuated
the association with beta-carotene, while the association with vitamin C
remained unchanged. The results are consistent with those of other
investigations and provide support for a protective effect of vitamin C,
carotenoids, and other substances found in the same fruits and vegetables
against the development of invasive cervical cancer. However, the fact that the
associations were driven by relation in two of the study sites and among women
of higher socioeconomic status leaves open the possibility of selection bias or
effects of unidentified aspects of dietary patterns.

Several studies have correlated the excessive production of prostaglandins (PGs) with tumor promotion and the suppression of the immune response. Inhibition of PGs by pharmacological agents has been demonstrated to enhance immunocompetence, and to suppress growth of tumors in animals and humans. In this study we examined the effect of retinol (I), all-trans-retinoic acid (II),
N-(4-Hydroxyphenyl) retinamide (N-4-HPR) (III), canthaxanthin (CTX) (IV), and
beta-carotene (beta-CT) (V) on the bioconversion of 14C-arachidonic acid (AA) to PGE2 by squamous carcinoma cells of the tongue, SCC-25. Agents (I), (II), (III), (IV) inhibited while (V) stimulated PGE2 formation in a dose related manner. N-4-HPR was the most potent inhibitor of PGE2 synthesis. The data suggest that certain retinoids and carotenoids have the potential of inhibition of PG synthesis by oral squamous carcinoma cells. Inhibitory effects such as those
described here and antioxidant properties might in part contribute to the
antiinflammatory and anticarcinogenic activity of retinoids in vivo.

The purpose of this study was to extend the knowledge of the antitumor activity
of liposomes and to identify, for the first time, the antitumor effect of
liposomes with the antioxidant beta-carotene. The administration of the
carotenoid encapsulated in in liposomes has the advantages of quantitation,
facilitation, and most importantly an increased therapeutic response, resulting
in the accentuation of regression of carcinoma in the hamster pouch. Tumors
induced after the application of the carcinogen
7,12-dimethylbenz[alpha]anthracene (0.5%) were injected with liposomes composed of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine in a ratio of 1:1:1 (large unilamellar vesicles). Tumor-bearing animals were divided into four groups, each containing 10 hamsters. The group treated with the liposomes of beta-carotene exhibited a significantly lower tumor burden (approx 5,000-fold difference) than the control tumor group. Electron- and light-micrographic analyses were used to substantiate the gross observations of tumor regression. It was noted that the carcinoma cells endocytozed liposomes in increased numbers compared with normal mucosa treated with liposomes. In addition, non-tumor-bearing hamsters injected with beta-carotene liposomes or liposomes alone did not exhibit any pathological change to the normal mucosa. An inflammatory infiltrate consisting of mononuclear cells, mast cells, and some polymorphonuclear leukocytes was noted, and degranulating polymorphonuclear leukocytes and mast cells and eosinophils predominated in the tumor controls (7,12-dimethylbenz[alpha]anthracene treated only). Notably, not all areas of
degenerating dysplasia or early carcinoma exhibited a dense inflammatory
response adjacent to the mucosa after the injection of beta-carotene liposomes.
The results demonstrate a selective nontoxic therapy to regress experimental
oral cancer.

Dietary carotene intake during the year before diagnosis was estimated for 96
men with lung cancer, 75 men with other epithelial cancers, and 97 hospital
controls. Relative to those of men in the lowest third of carotene intake (less
than 1,683 micrograms/day), the smoking-adjusted odds ratios for men in the
middle (1,683-2,698 micrograms/day) and upper (greater than 2,698
micrograms/day) thirds of carotene intake were 0.67 and 0.45, respectively, for
lung cancer (one-sided test for trend, p = 0.048) and 0.63 and 0.65,
respectively, for other epithelial cancers (one-sided test for trend p = 0.074).
The protective effect of estimated dietary carotene intake was considerably
stronger than was the effect of total intake of carotene-rich vegetables and
fruits (grams per day), providing some evidence that the protective factor is
carotene itself rather than another component of vegetables and fruits.

Antioxidant activity of carotenoids in multilamellar liposomes assayed by
inhibition of formation of thiobarbituric acid-reactive substances was in the
ranking: lycopene> alpha-tocopherol > alpha-carotene > beta-cryptoxanthin >
zeaxanthin = beta-carotene > lutein. Mixtures of carotenoids were more effective
than the single compounds. This synergistic effect was most pronounced when
lycopene or lutein was present. The superior protection of mixtures may be
related to specific positioning of different carotenoids in membranes.

Annu Rev Nutr 1998;18:93-116
Dietary oxidative stress and the potentiation of viral infection.
Beck MA, Levander OA
Frank Porter Graham Child Development Center, University of North Carolina, Chapel Hill 27599-8180, USA. melinda_beck@unc.edu

Oxidative stress is implicated in the pathogenesis of several viral infections,
including hepatitis, influenza, and AIDS. Dietary oxidative stress due to either
selenium or vitamin E deficiency increases cardiac damage in mice infected with
a myocarditic strain of coxsackievirus B3. Such dietary oxidative stress also
allows a normally benign (i.e., amyocarditic) coxsackievirus B3 to convert to
virulence and cause heart damage. This conversion to virulence is due to a
nucleotide sequence change in the genome of the benign virus, which then
resembles more closely the nucleotide sequence of virulent strains. Although it
has been known for many years that poor nutrition can affect host response to
infection, this is the first report of host nutrition affecting the genetic
sequence of a pathogen. Further research is needed to determine whether poor
host nutrition plays any role in the emergence of new viral diseases via
alterations in he genotype of an infectious agent.