Azoreductase activity of Sprague Dawley and Wistar-derived rats towards both carcinogenic and non-carcinogenic analogues of 4-dimethylaminophenylazobenzene (DAB)

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Abstract
Azoreductase activity towards the hepatocarcinogen p -dimethylaminophenylazobenzene (DAB) and four analogues has been measured in vitro in the liver and caecum of Sprague Dawley (Alpk/SD) and Alderley Park (Alpk/AP Wistar-derived) rats. Two carcinogenic DAB analogues, 3'-methyl- p -dimethylaminophenylazobenzene (3M) and 6- p -dimethyl-aminophenylazobenzothiazole (6BT) and two non-carcinogenic analogues, 4-N-pyrrolidinylazobenzene (4N) and 5- p -dimethylaminophenylazoindazole (5I) have been examined. The azoreductase activity towards DAB of a 9000 g supernatant of liver homogenate was greater in the SD than the AP strain between 6 and 13 weeks of age, but comparable to that of AP rats at 4 weeks of age. The activity towards DAB fell in both strains with increasing age. Animals of both strains fed a riboflavin-low diet (2–3 mg kg −1 ) had reduced azoreductase activity with DAB when compared to a standard diet at all ages studied, although the difference was less marked in the AP rats. 3M and 4N were azoreduced by the livers of both strains of rat fed a standard diet at a rate of ∼ 50% of that of DAB, whereas 51 and 6BT were cleaved at a much lower rate (5–20%). All the chemicals were reduced by an oxygen-insensitive enzyme in the liver preparation, as has previously been reported for DAB. DAB, 3M and 6BT were reduced at a similar rate to each other by a fraction containing caecal contents, both in and between the two strains of rat. Similarly, 4N and 51 were reduced by a caecal preparation at a similar rate to each other in and between both strains of rat, but at a rate of only 30–50% that shown by DAB, 3M and 6BT. In contrast to the conditions required by the liver azoreductase enzyme, anaerobic conditions were required for maximal activity of the caecal preparation. Liver azoreductase activity towards all the DAB analogues was reduced in both strains of rat maintained on a riboflavin-low diet, while the caecal azoreductase activity was unaffected. Neither the activity profile observed in vitro in the liver nor the caecum was found to correlate with the relative carcino-genicity reported for these compounds, suggesting that other factors are more important in determining this toxicity for the series of azo chemicals examined in this study.

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