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.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000627:therapeutic use*; D005038:Ethylnitrosourea / Q000031:analogs & derivatives / Q000627:therapeutic use*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D008770:Methylnitrosourea; D051379:Mice; D008815:Mice, Inbred Strains; D009607:Nitrosourea Compounds / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D014599:Uterus / Q000187:drug effects
D000970:Antineoplastic Agents; D004967:Estrogens; D009607:Nitrosourea Compounds; D008770:Methylnitrosourea; D005038:Ethylnitrosourea