Effects of LS 1727, a nitrosocarbamate of 19-nortestosterone, on dimethylbenz(a)anthracene-induced mammary tumors in the rat

Abstract

LS 1727, a nitrosocarbamat of 19-nortestosterone, caused a dose-dependant retardation of growth of dimethylbenz(a)anthracene-induced mammary tumors in rats. LS 1727 had a more pronounced depressive effect on tumor growth and tumor DNA synthesis than 19-nortestosterone or CCNU. The uterine weight was increased and the ovarian weight decreased by LS 1727. The uptake of radioactivity in the tumors after injection of 3H -dihydrotestosterone was reduced by LS 1727 but not the radioactivity uptake after injection of 3H -estradiol- 17β or 3H -progesterone. There was no accumulation of radioactivity in the tumors after injection of 3H -LS 1727 labeled in the steroid moiety but the radioactivity concentration declined with time parallel with the decline in blood concentration. Thin layer chromatography revealed that LS 1727 is rapidly metabolized to 19-nortestosterone and polar metabolites. It is concluded that LS 1727 may have a cytostatic effect on the tumors owing to an action of the alkylating moiety of the compound. The cytostatic action may be enhanced by androgenic and estrogenic effects of the compound.