title: An oestradiol-linked nitrosourea and site-directed chemotherapy in mammary carcinoma.
abstract: The half-life, peak concentration, peak accumulation and tissue availability of the DNA-crosslinking nitrosourea 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine (CNC-alanine) and its oestradiol-linked derivate (CNC-alanine-oestradiol-17-ester) were studied in liver, lung, spleen, uterus and mammary carcinomas in female Sprague-Dawley rats with chemically induced mammary carcinomas. Compared with CNC-alanine, the ester had a longer half-life, higher peak concentration, increased peak accumulation and enhanced tissue availability in all tissues. In oestradiol receptor positive mammary carcinomas, the oestradiol-linked drug showed a 2 times higher peak concentration, a 5 times longer half-life, a 10 times increased peak accumulation and a 20 times greater tissue availability compared with CNC-alanine. Oestradiol-linked nitrosoureas may offer new perspectives for site-directed chemotherapy of oestradiol receptor positive breast cancer.
authors: Institute for Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.
authors: B
authors: B
authors: Betsch
authors: M R
authors: MR
authors: Berger
authors: B
authors: B
authors: Spiegelhalder
authors: D
authors: D
authors: Schmähl
authors: G
authors: G
authors: Eisenbrand
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004958:Estradiol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D009588:Nitrogen Mustard Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; D004958:Estradiol; C058788:N-(2-chloroethyl)-1-nitrosocarbamoylalanine; C056364:1-(2-chloroethyl)-1-nitrosocarbamoylalanine estradiol-17-ester; D000409:Alanine