Mechanism of inhibition of estrogen-induced renal carcinogenesis in male syrian hamsters by vitamin C Article

Liehr, JG, Roy, D, Gladek, A. (1989). Mechanism of inhibition of estrogen-induced renal carcinogenesis in male syrian hamsters by vitamin C . CARCINOGENESIS, 10(11), 1983-1988. 10.1093/carcin/10.11.1983

cited authors

  • Liehr, JG; Roy, D; Gladek, A

authors

abstract

  • Dietary supplementation of vitamin C to diethylstilbestrol (DES)- or estradiol-treated male Syrian hamsters is known to inhibit renal carcinogenesis by ∼50%. To elucidate the mechanism of inhibition, the influence of administration of vitamin C on a series of previously described biochemical markers of kidney carcinogenesis was investigated. Hamsters were stratified into four groups: (i) untreated controls; (II) vitamin C-treated; (iii) estrogen-treated; and (iv) estrogen plus vitamin C-treated animals. Concomitant administration of vitamin C and diethylstilbestrol (DES) decreased concentrations of the major DES-DNA adduct by 70-90% in liver, kidney and testis than those receiving DES only. Diethylstilbestrol-4',4″-qulnone has previously been shown to be the genotoxic metabolite of DES responsible for DNA adduct formation in vivo. In vitro, vitamin C reduced diethylstilbestrol-4',4″-qulnone to cis- and trans-dlethylstllbestrol in a dose-dependent fashion. Changes in activities of quinone reductase, catalase, superoxide dismutase and of glutathione metabolizing enzymes (glutathione peroxidase, glutathione reductase, -γ-glutamyl transpeptidase and glucose-6-phosphate dehydrogenase) in response to vitamin C were not observed or not sufficiently large to account for the 50% decrease in tumor incidence. No differences were detected in indirect estrogen-induced kidney DNA adducts in response to vitamin C treatment. It is concluded that vitamin C inhibits estrogeninduced carcinogenesis by reducing concentrations of estrogen quinone metabolites and their DNA adducts. © 1989 IRL Press.

publication date

  • November 1, 1989

published in

Digital Object Identifier (DOI)

start page

  • 1983

end page

  • 1988

volume

  • 10

issue

  • 11