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.
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.
D000818:Animals; D002471:Cell Transformation, Neoplastic; D004260:DNA Repair / Q000187:drug effects; D004052:Diethylnitrosamine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005260:Female; D017313:Fenretinide; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009602:Nitrosamines / Q000633:toxicity*; D009924:Organ Culture Techniques; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000494:pharmacology
D009602:Nitrosamines; D017313:Fenretinide; D004052:Diethylnitrosamine; D014212:Tretinoin