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

Benzo[a]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, BP 7,8-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 pulinonary 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, support the idea that BP 7,8-oxide is a proximate carcinogenic metabolite of BP in the newborn mouse.