The tumorigenic activities of 6-nitrochrysene and its metabolites were evaluated in the newborn mouse model. Groups of mice were treated with the appropriate compounds in DMSO by i.p. injections on the 1st, 8th and 15th day of life. Seven hundred nmol/mouse of 6-nitrochrysene induced significant incidences and multiplicities of lung tumors in both sexes; only males were susceptible to liver tumor induction. At 100 nmol/mouse, 6-nitrochrysene had significant tumori-genicity in both lung and liver but was less active than at the higher dose. Administration of 100 nmol/mouse of 6-nitrochrysene, only on day 1, caused about the same tumor yield as was observed after treatment with 700 nmol/mouse given over 3 days. Among the metabolites of 6-nitrochrysene which were tested at 100 nmol/mouse, 6-nitrosochrysene and 6-aminochrysene were significantly less active in the lung and in the liver than 6-nitrochrysene. In the lung and trans-1, 2-dmydro-ld1hyd xy-6-nitn chrysene and trans-l, 2-dihydro-l, 2-dihydroxy-6-aminochysene had activities comparable to those observed in mice treated with equimolar doses of 6-nitrochrysene. In the liver, trans-l, 2-dihydro-l, 2-dihydroxy-6-nitrochrysene was more active than 6-nitrochrysene based on the number of tumors per mouse. These observations support our hypothesis that 6-nitrochrysene is metabolically activated by ring-oxidation to trans-1, 2-dihydro-1, 2-dihydroxy-6-nitrochrysene, followed by nitro-reduction to trans-1, 2-dihydro-1, 2-dihydroxy-6-amino-chrysene and, finally, oxidation to a diol-apoxide.
Bibliographical noteFunding Information:
This study was supported by National Cancer Institute Grant CA 35519. This is paper No. 122 of the series A Study of Chemical Carcinogenesis.