Mutagenicities of N-acyl-N-arylhydroxylamines for Salmonella.
The N-formyl, N-acetyl and N-propionyl derivatives of N-hydroxy-trans-4-aminostilbene (N-OH-AS), N-hydroxy-4-aminobiphenyl (N-OH-ABP) and N-hydroxy-2-aminonaphthalene (N-OH-AN) were synthesized and examined for their mutagenicities in Salmonella typhimurium TA 98. The N-formyl derivatives were direct-acting mutagens possibly due to hydrolysis, either spontaneously or by bacterial enzymes to hydroxylamines. Their mutagenicities were enhanced by rat liver microsomes and cytosol. All acetyl and propionyl derivatives required activation by either liver cytosol or microsomes. NADPH slightly decreased the microsome-mediated mutagenicities of the N-acyl derivatives of N-OH-AN. However, it greatly enhanced the cytosol-mediated mutagenicities of these hydroxamic acids, probably due to stabilization of their hydroxylamine derivatives. The mutagenicities reported here do not correlate with previously reported carcinogenicity data. Thus, data obtained in Salmonella mutagenicity studies may not necessarily directly reflect carcinogenic potential in mammalian systems due to the different mechanisms of activation.
Wang
C Y
CY
Department of Chemical Carcinogenesis, Michigan Cancer Foundation, Detroit 48201.
Linsmaier-Bednar
E M
EM
Lee
M S
MS
King
C M
CM
D000611:Aminobiphenyl Compounds / Q000633:toxicity*; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006898:Hydroxylamines / Q000633:toxicity*; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects*; D009249:NADP / Q000378:metabolism; D009281:Naphthalenes / Q000633:toxicity; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics; D013267:Stilbenes / Q000633:toxicity*; D013329:Structure-Activity Relationship
D000611:Aminobiphenyl Compounds; D006898:Hydroxylamines; D009281:Naphthalenes; D013267:Stilbenes; C031721:naphthalene; D009249:NADP