The disposition and in vivo covalent binding to liver DNA of the monoazodyes 6-(p-dimethylaminophenylazo)benzothiazole (6BT) and 5-(p-dimethylaminophenylazo)indazole (5I) after administration to the rat.
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abstract
6-(p-Dimethylaminophenylazo)benzothiazole (6BT) and 5-(p-dimethylaminophenylazo)indazole (5I) comprise respectively a carcinogen/non-carcinogen pair of monoazo dyes related to the hepatocarcinogen, butter yellow (DAB). While both members of the pair are potent bacterial mutagens in vitro, only 6BT induces unscheduled DNA synthesis in rat liver in vivo. To investigate factors responsible for these divergent activities we have determined in rats: relative rates of uptake from the gut after direct injection of 14C-labelled compound into intestine in situ, and after administration p.o.; distribution in selected tissues and elimination in urine, faeces and bile; binding of both compounds in vivo to liver DNA. The results revealed that, although 5I was taken up from the gut to a lesser extent than 6BT, comparable labelling associated with both compounds was detected in the presumed target organ (the liver). 5I binds in vivo to DNA much less effectively than 6BT. Therefore it would seem that other factors, such as differential metabolism in vivo, are more important than differences in uptake and distribution in accounting for the divergent activities of 6BT and 5I.
