DNA Adduct Measurements in Relation to Small Intestine and Forestomach Tumor Incidence during the Chronic Feeding of Coal TAR or Benzo[A]Pyrene to Mice

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Abstract In a two-year carcinogenicity bioassay, female B6C3F1 mice were fed up to 100 ppm benzo[a]pyrene (BaP) or up to 1% coal tar in the diet. Forestomach tumors were induced in mice fed BaP, with the incidence increasing sharply between 5 and 25 ppm Bap. Forestomach tumors were also observed in mice fed coal tar, with a pronounced increase at the 0.3% dose. The incidence of forestomach tumors was approximately the same at 0.3% and 0.6% coal tar, but declined at the 1.0% dose, due to early mortality from a high incidence of small intestine adenocarcinomas. DNA adduct levels were examined in the forestomachs and small intestines after feeding BaP or coal tar for 4 weeks. In BaP-treated mice, one major adduct was observed; this adduct accounted for 7-15% of the forestomach adducts in mice fed coal tar. A dose-related increase was observed in adduct levels in the forestomachs of BaP-and coal tarfed mice. The induction of forestomach tumors from BaP or coal tar was associated with the same levels of BaP-DNA adducts. In the small intestines, total adduct levels increased up to the 0.6% coal tar dose and then decreased at the 1.0% dose. Since the tumor incidence was highest at the 1.0% dose, coal tar-induced cytotoxicity and cell proliferation may be critical factors in tumor induction in this tissue.