Mutagenicity of four homo-aza-steroidal esters of m-N,N-bis(2-chloroethyl)aminocinnamic acid in the Ames test.
Four new chemicals, the homo-aza-steroidal esters of m-N,N-bis(2-chloroethyl)aminocinnamic acid, originaly synthesized to be used as antineoplastic agents, were tested for their mutagenic activity in the Ames test. 3 beta-Hydroxy-13 alpha-amino-13,17-seco-5-androsten-17-oic-13,17- lactam ester (ACALE3) and 3 alpha-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam ester of m-N,N-bis(2-chloroethyl)aminocinnamic acid (ACALE4) were found to induce base-pair substitutions, causing dose-dependent increases in his+ revertants in strains TA100 and TA1535, while no dose-dependent relations were established when 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam ester (ACALE1) and 17 beta-hydroxy-3-aza-A-homo-4 alpha-androsten-4-one ester of m-N,N-bis(2-chloroethyl)aminocinnamic acid (ACALE2) were tested. The presence of metabolic activation enzymes in the test system had no effect in his+ revertants in strains TA100 and TA1535. The chemicals tested although having the same alkylating moiety and a similar chemical structure exhibited different mutagenic activities.
Voutsinas
G
G
Institute of Biology, National Research Center Democritus, Aghia Paraskevi Attikis, Athens, Greece.
Kappas
A
A
Demopoulos
N A
NA
Camoutsis
C
C
D000731:Androstanes / Q000633:toxicity*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002934:Cinnamates / Q000633:toxicity*; D066298:In Vitro Techniques; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D017354:Point Mutation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium / Q000187:drug effects
D000731:Androstanes; D000970:Antineoplastic Agents; D002934:Cinnamates; D009153:Mutagens