title: Mutagenic activity of the antitumour agent homo-aza-steroidal ester of p-N,N-bis(2-chloroethyl)aminophenoxyacetic acid (NSC 294859) in the Salmonella/microsome assay.
abstract: The mutagenic activity of the new antitumour agent 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam- p-N,N-bis(2-chloroethyl)aminophenoxyacetate (NSC 294859) was studied in the Salmonella/microsome assay. It was found to induce base pair substitutions, causing dose-dependent increases in his+ revertants in strains TA100 and TA1535. The alkylating moiety, p-N,N-bis(2-chloroethyl)-aminophenoxyacetic acid, was shown to be less effective than the parent compound, while the modified steroid moiety, 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam, showed no mutagenic effect in all strains used. The presence of metabolic activation enzymes in the test system induced a further increase in his+ revertants in strains TA100 and TA1535, in both the parent compound and the alkylating moiety of the parent compound, while it had no effect in the case of the steroidal lactam.
authors.affiliation: Institute of Biology, National Research Center Democritus, Aghia Paraskevi Attikis, Athens, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Voutsinas
authors.forename: A
authors.initials: A
authors.lastname: Kappas
authors.forename: N A
authors.initials: NA
authors.lastname: Demopoulos
authors.forename: P
authors.initials: P
authors.lastname: Catsoulacos
mesh_terms: D000731:Androstanes / Q000633:toxicity; D000970:Antineoplastic Agents / Q000633:toxicity*; D001378:Azasteroids / Q000633:toxicity; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000235:genetics; D016368:Frameshift Mutation; D008110:Liver Extracts; D008862:Microsomes, Liver / Q000201:enzymology; D016296:Mutagenesis; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009588:Nitrogen Mustard Compounds / Q000737:chemistry / Q000633:toxicity*; D010642:Phenoxyacetates / Q000633:toxicity; D017354:Point Mutation; D015203:Reproducibility of Results; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
chemical_list: D000731:Androstanes; D000970:Antineoplastic Agents; D001378:Azasteroids; D004269:DNA, Bacterial; D008110:Liver Extracts; D009153:Mutagens; D009588:Nitrogen Mustard Compounds; D010642:Phenoxyacetates; C082605:4-N,N-bis(2-chloroethyl)aminophenoxyacetic acid; C036047:3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam; C038583:NSC 294859