Tumorigenicity of benzo[alpha]pyrene 4,5-,7,8-,9,10- and 11,12-oxides in newborn mice

Benzo[alpha]pyrene (BP) and its 4,5-,7,8-,9,10 and 11,12-oxides were tested for carcinogenicity by intraperitoneal injection into newborn mice. The mice were treated sequentially with 200, 400 and 800 nmol of hydrocarbon on days 1,8 and 15 of life, and the animals were killed at 24 weeks of age. Mice treated with BP, BP7,8-oxide and BP 11,12-oxide had a 93%, 72% and 20% incidence of pulmonary adenomas, respectively, with an average of 10.0, 2.1 and 0.32 adenomas/mouse, respectively. Eight percent of the control animals had pulmonary adenomas with an average of 0.08 adenomas per mouse. The moderate tumorigenic activity of the relatively unstable BP 7,8-oxide, together with earlier data on the strong carcinogenic activity of BP, 7,8-dihydrodiol, supports the idea that BP 7,8-oxide is a proximate carcinogenic metabolite of BP in the newborn mouse.