The in vivo and in vitro genotoxicity of aromatic amines in relationship to the genotoxicity of benzidine.
Benzidine and 12 related aromatic amines have been studied for the effects of substituent groups and pi orbital conjugation on their genotoxicity as measured by their mutagenicity in vitro with Salmonella and by chromosomal aberrations (CA) in vivo in the bone-marrow cells of mice. The in vitro studies indicated increases in mutagenicity with increases in the electron withdrawing ability of para' substituents. Mutagenicity also increases with increased conjugation as shown by the degree of planarity of the biphenyl compounds and by comparing the mutagenicities of biphenyl amines to stilbenes as well as to ethylene bridged diphenyl compounds. The relative in vitro mutagenicity results were not predictive of relative in vivo CA results. The 3 most genotoxic compounds in vivo were the conjugated amines without substituents in the para' position. The CA values for 4-aminostilbene were exceptionally high. These in vivo results indicate increased genotoxicity for benzidine analogs without substitution in the para' position.
Sinsheimer
J E
JE
College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
Hooberman
B H
BH
Das
S K
SK
Brezzell
M D
MD
You
Z
Z
D000611:Aminobiphenyl Compounds / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D001560:Benzidines / Q000633:toxicity; D001853:Bone Marrow / Q000187:drug effects; D002869:Chromosome Aberrations; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D016296:Mutagenesis; D009152:Mutagenicity Tests; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium; D013267:Stilbenes / Q000737:chemistry / Q000633:toxicity*; D013329:Structure-Activity Relationship
D000611:Aminobiphenyl Compounds; D001560:Benzidines; D013267:Stilbenes; C029876:benzidine; C016228:4-aminostilbene