Tumorigenicity and metabolism of 1-nitropyrene in A/J mice

Abstract

Four groups of 28-32 male and female A/J mice were given i.p. injections of either trioctanoin or 1-nitropyrene in trioctanoin such that the total doses of 1-nitropyrene were 0.71 mmol/kg, 2.14 mmol/kg, or 6.44 mmol/kg. The mean number of lung tumors/mouse was 1.3 .+-. 1.0 in the group treated with 6.44 mmol/kg of 1-nitropyrene compared with 0.3 .+-. 0.6 in the trioctanoin group (P < 0.001). Combined tumor incidence was not significant compared with controls in the 2 lower dose groups. Cultured explants of A/J mouse lung, and 9000 g supernatant of A/J mouse lung and liver, metabolized [14C] 1-nitropyrene to 4,5-dihydro-4,5-dihydroxy-1-nitropyrene and 1-nitrohydroxypyrenes. Substantial amounts of unknown polar metabolites were also produced by cultured lung. Nitro-reduction to 1-aminopyrene was minimal in mouse lung and liver, even under O-deficient conditions.