Evaluation of new estrogen-linked 2-chloroethylnitrosoureas. I. Short term anticancer efficacy in methylnitrosourea-induced rat mammary carcinoma and hormonal activity in mice.

Short-term treatment of N-methyl-N-nitrosourea-induced mammary carcinomas in Sprague-Dawley rats with estradiol-linked nitrosoureas shows that the compounds in which the cytotoxic group is linked to position 17 of estradiol are superior to the 3-ester analogue. Moreover, N-(2-chloroethyl)-N-nitroso-carbamoyl (CNC)-L-alanyl-L-alanine-estradiol-3-ester is more effective and less toxic than CNC-L-alanine-estradiol-3-ester, being equivalent to ovariectomy in its therapeutic efficacy. Unlinked CNC-amino acid or-dipeptide in admixture with estradiol is less effective. Linked compounds at therapeutic dosages display estrogenic activity.