Comparative tumorigenicity of 6-nitrochrysene and its metabolites in newborn mice

The tumorigenic activities of 6-nitrochrysene and its metaboliteswere evaluated in the newborn mouse model. Groups of mice weretreated with the appropriate compounds in DMSO by i.p. injectionson the 1st, 8th and 15th day of life. Seven hundred nmol/mouseof 6-nitrochrysene induced significant incidences and multiplicitiesof lung tumors in both sexes; only males were susceptible toliver tumor induction. At 100 nmol/mouse, 6-nitrochrysene hadsignificant tumori-genicity in both lung and liver but was lessactive than at the higher dose. Administration of 100 nmol/mouseof 6-nitrochrysene, only on day 1, caused about the same tumoryield as was observed after treatment with 700 nmol/mouse givenover 3 days. Among the metabolites of 6-nitrochrysene whichwere tested at 100 nmol/mouse, 6-nitrosochrysene and 6-aminochrysenewere significantly less active in the lung and in the liverthan 6-nitrochrysene. In the lung and trans-1, 2-dmydro-ld1hydxy-6-nitn chrysene and trans-l, 2-dihydro-l, 2-dihydroxy-6-aminochysenehad activities comparable to those observed in mice treatedwith equimolar doses of 6-nitrochrysene. In the liver, trans-l,2-dihydro-l, 2-dihydroxy-6-nitrochrysene was more active than6-nitrochrysene based on the number of tumors per mouse. Theseobservations support our hypothesis that 6-nitrochrysene ismetabolically activated by ring-oxidation to trans-1, 2-dihydro-1,2-dihydroxy-6-nitrochrysene, followed by nitro-reduction totrans-1, 2-dihydro-1, 2-dihydroxy-6-amino-chrysene and, finally,oxidation to a diol-apoxide.