N-Nitrosodiethylamine-induced nodule-like alveolar lesion and its prevention by a retinoid in BALB/c mouse mammary glands in the whole organ in culture.

Abstract

The ability of N-nitrosodiethylamine (DENA) to induce transformation of the mammary cells was studied in culture of the whole mammary organ from BALB/c female mice. Incidence of nodule-like alveolar lesions (NLAL) in the glands in vitro has been as a measure of transformation. NLALs are analogous to the precancerous hyperplastic alveolar nodules (HAN) of mouse mammary gland in vivo. The mammary glands were treated with graded concentrations (0.1-2.5 microgram/ml) of DENA during lobuloalveolar morphogenesis in medium (Waymouth's MB752/1) containing insulin, prolactin, hydrocortisone and aldosterone. DENA treatment caused a dose-related increased occurrence of NLAL in the glands in vitro and concentration of 1.5 microgram/ml produced the highest incidence of 85%. The high incidence of NLAL was accompanied by a 3-fold increase of DNA repair activity in the DENA treated glands. Incubation of the glands for 6 days after DENA treatment in medium containing N-4-hydroxyphenyl)retinamide and the same hormone mixture caused 61% inhibition of NLAL incidence. The results indicate that DENA is capable of inducing a high level of transformation of the mammary epithelial cells in vitro and that this retinoid can inhibit expression of the transformed cells acting at the promotional level.