Selenium mediated dose-inhibition of 7,12-dimethylbenz[ a]anthracene-induced transformation of mammary cells in organ culture

Abstract

Influence of selenium (sodium selenite, Na 2SeO 3) on transformation of mammary cells, induced by 7,12-dimethylbenz[ a]anthracene (DMBA) was assessed in organ culture of the whole mammary glands from BALB c female mice. Transformation was determined by the presence of nodule-like alveolar lesions (NLAL) induced by DMBA in the glands in vitro. Selenium at concentrations of 10 −8 M and 10 −7 M enhanced the transformation frequency of the glands, acting both at the ‘initiation’ and ‘promotional’ stages. The enhancement was notable both by scoring the frequency of glands with NLAL and the number of NLAL per gland. At selenium concentration of 10 −5 M a modest 18% inhibition of the frequency of transformed glands was detectable at the initiation stage. At promotional stage 10 −6 M selenium caused a 37% inhibition of the frequency of transformed glands and at the same stage, an 84% inhibition was present at 10 −5 M concentration of selenium in the medium. The concentration of 10 −4 M was toxic to the glands in vitro. The inhibition of the frequency of the transformed glands was accompanied by a pronounced reduction of the number of NLAL per gland. Thus, selenium is capable of causing a dose-dependent inhibition of transformation of mammary epithelial cells in organ culture, acting mostly at the promotional stage of the process. Selenium appears to act by preventing expression of the transformed cells as ‘high risk’, potentially neoplastic lesions in the glands in vitro. The present findings thus provide an in vitro model for future studies on the mechanism of selenium mediated chemoprevention of the neoplastic process.