Use of an in vivo/in vitro rat liver DNA repair assay to predict the relative rodent hepatocarcinogenic potency of 3 new azo mutagens

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Abstract
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-β-cyanoethyl-N-methylamino)-phenylazo]benzthiazole; CNEt6BT). The order of relative carcinogenic potency predicted by the Salmonella mutation data was CNEt6BT >> MA6BT=6BT >> 6PT. In contrast, that inferred from the in vivo liver DNA repair data was MA6BT > 6BT >> CNEt6BT >>6PT. This divergence of predictions is discussed in terms of the differing solution properties of the four test chemicals.

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