Tumor initiating activities of 1-nitropyrene and its nitrated products in SENCAR mice

The environmental mutagens, 1-nitropyrene, 1,3-dinitropyrene, 1,6-dinitropyrene and 1,8-dinitropyrene were evaluated for their ability to initiate skin tumors in male and female SENCAR mice. 1-Nitropyrene (greater than 99.5% purity) did not induce papilloma formation over a dose range of 0-3.0 mg/mouse after 30 weeks of promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). Systemic administration of 1-nitropyrene by i.p. injection over a dose range of 0-8.0 mg/mouse followed by topical treatment with TPA also did not induce papilloma formation. A mixture of dinitropyrenes (1,3-dinitropyrene, 1,6-dinitropyrene and 1,8-dinitropyrene (1:1.94:1.95] (99% purity) was dermally applied to SENCAR mice over a dose range of 0-2.0 mg/mouse and the mice subsequently promoted with TPA. A significant induction of papillomas was observed at 30 weeks (0.37-0.39 papillomas/mouse, 26-29% of the mice bearing tumors) at 2.0 mg/mouse. Comparison of this data with that obtained from the same mouse strain using diesel exhaust particulate extracts containing 1-nitropyrene and its nitrated products indicate that these nitrated polynuclear aromatics do not significantly contribute to the mouse skin tumorigenic activity of diesel exhaust particulate extracts.