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Wide-Range Linear Dose-Response Curve for DNA Binding of Orally Administered Benzo(a)pyrene in Mice¹

Environmental Carcinogenesis Unit, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada V5Z 1L3

The binding of p.o. benzo(a)pyrene (BP) to the DNA of mice was investigated. With a single dose of 1 µg, levels of DNA binding were highest in the liver, followed by the intestine, colon, and stomach. In all organs, the majority of DNA-associated radioactivity was in the form of adducts which did not release ethyl acetate-soluble BP tetrols on acid hydrolysis. In both stomach and liver, the formation of acid-hydrolyzable and non-acid-hydrolyzable BP-DNA adducts was linearly related to dose, over a carcinogen dosage range of 10^-8 to 10^-3 g (liver) or 10^-7 to 10^-3 g (stomach). Repair or removal via cell turnover of liver BP-DNA adducts over a period of 7 days proceeded with the same efficiency when the dose of the administered carcinogen was varied over a range of 100,000-fold. These results suggest that in vivo the initial interaction between DNA and ingested BP takes place in the same manner both at high doses typical of laboratory carcinogenesis experiments and at low doses typical of human exposure.

¹ This work was supported by Health and Welfare Canada, Grant 6610-1138-52. Presented, in part, at the Sixth International Symposium on Polynuclear Aromatic Hydrocarbons, Columbus, Ohio, October 1981 (17).

² Research Scholar, Health and Welfare Canada.

Received 11/11/82. Accepted 3/ 8/83.