Mutagenicity of N-substituted phenanthrene 9,10-imines in Salmonella typhimurium and Chinese hamster V79 cells.
We previously showed that some (nonsubstituted) aziridines derived from polycyclic aromatic hydrocarbons (arene imines) elicit various mutagenic and genotoxic effects in bacteria and mammalian cells and that these arene imines are active at much lower concentrations than the corresponding epoxide analogues. In the present study, N-substituted derivatives of phenanthrene 9,10-imine were investigated. All 10 derivatives studied showed direct mutagenicity in Salmonella typhimurium TA100. Some of the compounds additionally exhibited weak effects in the strains TA98 and TA1537. Most N-substituted derivatives were weaker mutagens than unsubstituted phenanthrene 9,10-imine but stronger mutagens than phenanthrene 9,10-oxide. Bulky substituents reduced the mutagenicity more than did small substituents. In addition, the derivatives with electron-withdrawing substituents (with the exception of N-chlorophenanthrene 9,10-imine) were weaker mutagens than those with electron-donating substituents. Phenanthrene 9,10-imine and five N-substituted derivatives were investigated to determine whether they induce gene mutations at the hgprt locus in V79 cells. Four compounds, including the parent aziridine, were positive in the V79 test. The other two compounds were negative. The mutagenic potencies in the V79 cell system did not correlate well with those obtained with the Salmonella system. Overall, the study shows that in addition to unsubstituted arene imines, N-substituted derivatives are mutagenic. This finding is of interest, as metabolic pathways leading from aromatic compounds to N-substituted arene imines are conceivable.
D000818:Animals; D001388:Aziridines / Q000633:toxicity*; D001389:Azirines / Q000633:toxicity*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens; D010616:Phenanthrenes / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000235:genetics; D013329:Structure-Activity Relationship
D001388:Aziridines; D001389:Azirines; D009153:Mutagens; D010616:Phenanthrenes; C046665:9,10-epoxy-9,10-dihydrophenanthrene; C050776:phenanthrene 9,10-imine