Coadministration of vitamin C to estrogen-treated Syrian hamsters significantly lowered the incidence of estradiol-induced renal carcinoma.
The aim of the proposed study is the elucidation of the mechanism of action of vitamin C in this tumor model. The knowledge of how vitamin C inhibits estrogen-induced carcinogenesis will benefit in two ways: 1. It will aid in understanding the mechanism of tumorigenesis by estrogens. 2. The use of vitamin C to inhibit tumor formation may have a more general preventative value in other tumors as well. It is suspected that vitamin C administration to estrogen-treated Syrian hamsters in some unknown way influences estrogen metabolism and thus prevents cellular damage by reactive estrogen metabolites. This hypothesis will be tested in the following way: 1. Estradiol metabolic profiles of chronically estradiol-treated Syrian hamsters with or without coadministration of vitamin C will be examined. Metabolite profiles will be examined for any evidence of reduction of quinone/semiquinone metabolites by vitamin C. 2. The influence of vitamin C treatment in vivo on estradiol-induced DNA adduct profiles will be studied. 3. The influence of vitamin C treatment in vivo on repair of estrogen-induced DNA adducts will be investigated. 4. The activity of estradiol 2/4 hydroxylase in estrogen-treated hamsters under influence of vitamin C will be tested. 5. The influence of vitamin C treatment on prostaglandin endoperoxide synthase in hamster kidney will be studied. 6. Activity levels of superoxide dismutase and also glutathione transferase will be measured in estrogen-treated animals with or without coadministration of vitamin C.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA044069-03
Application #
3186614
Study Section
Metabolic Pathology Study Section (MEP)
Project Start
1986-09-01
Project End
1989-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
Liehr, J G (1991) Vitamin C reduces the incidence and severity of renal tumors induced by estradiol or diethylstilbestrol. Am J Clin Nutr 54:1256S-1260S
Gladek, A; Liehr, J G (1991) Transplacental genotoxicity of diethylstilbestrol. Carcinogenesis 12:773-6
Roy, D; Weisz, J; Liehr, J G (1990) The O-methylation of 4-hydroxyestradiol is inhibited by 2-hydroxyestradiol: implications for estrogen-induced carcinogenesis. Carcinogenesis 11:459-62
Liehr, J G; Roy, D; Ari-Ulubelen, A et al. (1990) Effect of chronic estrogen treatment of Syrian hamsters on microsomal enzymes mediating formation of catecholestrogens and their redox cycling: implications for carcinogenesis. J Steroid Biochem 35:555-60
Liehr, J G; Roy, D (1990) Free radical generation by redox cycling of estrogens. Free Radic Biol Med 8:415-23
Liehr, J G (1990) Genotoxic effects of estrogens. Mutat Res 238:269-76
Roy, D; Liehr, J G (1989) Changes in activities of free radical detoxifying enzymes in kidneys of male Syrian hamsters treated with estradiol. Cancer Res 49:1475-80
Liehr, J G; Roy, D; Gladek, A (1989) Mechanism of inhibition of estrogen-induced renal carcinogenesis in male Syrian hamsters by vitamin C. Carcinogenesis 10:1983-8
Roy, D; Bui, Q D; Weisz, J et al. (1989) Comparison of assays for catechol estrogen synthase activity: product isolation vs radioenzymatic catechol-O-methyltransferase-coupled procedures. J Steroid Biochem 33:243-9
Roy, D; Liehr, J G (1989) Metabolic oxidation of diethylstilbestrol to diethylstilbestrol-4',4""-quinone in Syrian hamsters. Carcinogenesis 10:1241-5

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