In vitro and in vivo effects of sodium selenite on 7,12-dimethylbenz[a]anthracene-DNA adduct formation in isolated rat mammary epithelial cells

Supplementation with increasing quantities of selenium (Se), as sodium selenite, to cultures of rat mammary epithelial cells resulted in a proportional depression in 7,12-dimethylbenz[a]anthracene (DMBA) binding to DNA. A depression in the two major anti bay-region dihydrodiol epoxide-deoxyribonucleoside adducts largely accounted for the reduced binding. DMBA-DNA binding in freshly isolated mammary cells from rats fed a diet containing 2.0 p.p.m. Se and incubated in culture with DMBA for 24 h was decreased 32% compared to binding in cells obtained from rats fed 0.1 p.p.m. Se. DMBA-DNA binding in mammary cells obtained from rats fed supplemental Se for 2 weeks or more was depressed compared to that occurring in cells from unsupplemented rats. The reduced ability of cells obtained from rats previously fed a 2.0 p.p.m. Se diet to activate DMBA to intermediates capable of binding to DNA became increasingly apparent with the duration of exposure to the carcinogen. Consistent with the in vitro supplementation study, cells isolated from rats previously fed a diet containing 2.0 p.p.m. Se had a reduced occurrence of the two major anti dihydrodiol epoxide adducts. The depression in DMBA binding following selenite supplementation, both in vitro and in vivo, supports the ability of Se to inhibit the initiation phase of carcinogenesis.