Brief Communication: Antitumor Action of Vitamin A in Mice Inoculated With Adenocarcinoma Cells2

Rettura, G; Schittek, Anton; Hardy, Mark A.; Levenson, Stanley Μ.; Demetriou, Achilles A.; Seifter, Eli

doi:10.1093/jnci/54.6.1489

Cited by 53 publications

(18 citation statements)

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“…antitumor immunity in vivo, detected in mice immunized with syngeneic tumors and subse- quently challenged with viable cells of the immunizing tumor, was substantially increased in mice that had been fed a diet enriched in VAOAc. These results could explain previous reports of inhibition of the growth and development, or even regression, of various tumors in animals treated with retinoids or carotenoids (37)(38)(39)(40)(41) and also are compatible with epidemiological data showing that human cancer risks are inversely correlated with blood retinol and with dietary /carotene (42). To study the possible immunopotentiating effect of VAOAc, we used two cloned sarcoma cell lines, one of them (HT3-2.…”

Section: Discussionsupporting

confidence: 91%

Enhancement of specific antitumor immunity in mice fed a diet enriched in vitamin A acetate.

Malkovský¹,

Doré²,

Hunt³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

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Age-matched male CBA mice on a conventional or a vitamin A acetate (VAOAc)-rich diet were immunized with irradiated cloned 3-methylcholanthrene-or Harvey sarcoma virus-induced (McSa-I or HT3,2.1) sarcoma cells and then challenged with viable corresponding or unrelated (non-crossreacting) syngeneic sarcoma cells. The survival, of the specifically immunized mice on the VAOAc diet was significantly prolonged in comparison with all control groups of mice as assessed by using logrank tests. Moreover, the specific immunization markedly decreased the incidence of tumors after the McSa-1 (but not HT3-2.1) challenge in a group of mice on the VAOAc diet (5% tumor incidence) compared with-the equivalent group on the control diet (50% tumor incidence). Neither the VAOAc diet nor in vivo immunization alone or combined influenced. natural-killer cell. activity. Specific T-cell-mediated cytotoxicity after in vivo priming and in vitro boosting with sarcoma cells was increased in VAOAcfed mice. However, the marginal increase in cytotoxicity does not in itself explain the strikingly increased resistance to tumor transplants in preimmunized mice on the VAOAc diet in comparison with preimmunized mice on the control diet. The results indicate that a diet enriched in VAOAc can modify the ability of the immune system of a mouse to respond effectively to tumor antigens and can influence whether a tumor grows or regresses.A connection between the risk of cancer and a substance discovered in the beginning of this century (1-4) and subsequently named vitamin A (5) was revealed in 1926 when susceptibility to carcinomas of the stomach in rats fed a vitamin Adeficient diet was observed (6). Since that time, a vast literature suggesting that vitamin A and retinoids (naturally occurring and synthetic derivatives of vitamin A) generally retard or prevent malignant transformation, suppress tumor promotion, or even cause reversion of transformed cells and regression of certain tumors has accumulated (reviewed in refs. 7 and 8). The mechanisms of these manifold anticancer effects are still conjectural (7,8). However, re-tinoid substances can also act as potent immunoregulatory agents (9-18). It has been proposed, but not supported experimentally, that, besides any direct anticancer activity retinoids might exercise, their antitumor effect might be an outcome of the enhancement of host antitumor immune responses (18)(19)(20)(21).This view has been upheld by in vitro studies by Dennert et al. (22) who have shown an augmented antitumor cytotoxic activity of splenic T lymphocytes in mice injected with retinoic acid. Moreover, using the tumor-cell neutralization (Winn)

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Section: Discussionsupporting

confidence: 91%

Enhancement of specific antitumor immunity in mice fed a diet enriched in vitamin A acetate.

Malkovský¹,

Doré²,

Hunt³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

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“…Thus, treatment with the steroid for 1 day or more resulted in a significant involution of the organ and a marked decrease in its vitamin A content. It is noteworthy that a decrease in the plasma concentration of vitamin A and in the amounts in the adrenals and thymus has also been reported in mice subjected to phys ical stress by the application of a partial body cast to the thorax for 3 days [8]. As in the present study the greatest loss of vitamin A occurred from the thymus [8],…”

Section: Discussionsupporting

confidence: 81%

“…Experimental studies have shown that physical stress precipitates frank vitamin A deficiency in rats on a marginal intake of the vitamin [9], possibly as a result of stressmediated tissue depletion [8]. It is probable that stress-induced secretion of corticoste roids reduces tissue vitamin A by favouring its elimination from the body.…”

Section: Introductionmentioning

confidence: 99%

Effect of Corticosterone on the Plasma and Tissue Concentrations of Vitamin A in Rats

Atukorala

Basu

Dickerson³

1981

Ann Nutr Metab

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The administration of large doses of corticosterone to normal adult male rats resulted in a rapid loss of vitamin A from the plasma, liver, adrenals and thymus. Of the organs studied, the thymus appeared to be the most sensitive to treatment. The steroidmediated depression of plasma and tissue contents of vitamin A was reversed when animals were treated with corticosterone in combination with vitamin A.

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“…Retinoic acid and retinol inhibit the growth of of MCF-7, Hs578T, and ZR-75-B cell lines. Retinoic acid is more potent than retinol in this regard: 50% growth inhibition is achieved by 6 nM retinoic acid in ZR-75-B and by 700 nM in MCF-7 and Hs578T, whereas [5][6][7][8] ,M retinol is required in all three cell lines. The time to onset of growth inhibition varies markedly between cell lines and is not related to.…”

mentioning

confidence: 99%

“…Recent studies have examined possible interactions between retinoids and breast cancer. Several retinoids have been shown to inhibit rat mammary carcinogenesis induced by 7,12-dimethylbenz(a)anthracene and by N-methyl-N-nitrosourea (4-7), and to decrease the initial tumor growth rate of a transplantable mammary adenocarcinoma in mice (8). Lotan and Nicolson reported growth inhibitory effects of retinoic acid and retinyl acetate in vitro on several rat, murine, and human mammary cancer cell lines (9, 10).…”

mentioning

confidence: 99%

Binding of Retinoids to Human Breast Cancer Cell Lines and their Effects on Cell Growth

1980

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Brief Communication: Antitumor Action of Vitamin A in Mice Inoculated With Adenocarcinoma Cells2

Cited by 53 publications

References 0 publications

Enhancement of specific antitumor immunity in mice fed a diet enriched in vitamin A acetate.

Enhancement of specific antitumor immunity in mice fed a diet enriched in vitamin A acetate.

Effect of Corticosterone on the Plasma and Tissue Concentrations of Vitamin A in Rats

Binding of Retinoids to Human Breast Cancer Cell Lines and their Effects on Cell Growth

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