Use of an in vivo/in vitro rat liver DNA repair assay to predict the relative rodent hepatocarcinogenic potency of 3 new azo mutagens.
The in vivo/in vitro rat liver DNA repair assay described by Mirsalis and Butterworth has been employed to compare the relative genotoxicity to the rat liver of three mutagenic analogues of the potent rat hepatocarcinogen 6-dimethylamino-phenylazobenzthiazole (6BT). The compounds evaluated were 6BT, its monomethyl analogue (6-monomethylamino-phenylazobenzthiazole; MA6BT), an analogue in which the -NMe2 group of 6BT is replaced by a piperidinyl group (6-[4-N-piperidinylphenyl]azobenzene; 6PT) and the N-cyanoethyl analogue of MA6BT (6-[p-(N-beta-cyanoethyl-N-methylamino)-phenylazo]benzthiazole; CNEt6BT). The order of relative carcinogenic potency predicted by the Salmonella mutation data was CNEt6BT much greater than MA6BT = 6BT much greater than 6PT. In contrast, that inferred from the in vivo liver DNA repair data was MA6BT greater than 6BT much greater than CNEt6BT much greater than 6PT. This divergence of predictions is discussed in terms of the differing solution properties of the four test chemicals.
D000818:Animals; D001391:Azo Compounds / Q000633:toxicity*; D052160:Benzothiazoles; D002273:Carcinogens; D004260:DNA Repair / Q000187:drug effects*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects*; D008113:Liver Neoplasms / Q000139:chemically induced; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D009152:Mutagenicity Tests; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium; D013844:Thiazoles / Q000633:toxicity*; D004124:p-Dimethylaminoazobenzene / Q000031:analogs & derivatives* / Q000633:toxicity
D001391:Azo Compounds; D052160:Benzothiazoles; D002273:Carcinogens; D013844:Thiazoles; C012103:N,N-dimethyl-4-(6-benzothiazolylazo)aniline; C045232:6-(4-N-piperidinylphenyl)azobenzothiazole; C045233:6-(4-(N-2-cyanoethyl-N-methylamino)phenylazo)benzothiazole; C045234:6-monomethylaminophenylazobenzothiazole; D004124:p-Dimethylaminoazobenzene