||Health Effects Research Lab., Research Triangle Park, NC. Genetic Toxicology Div. ;Environmental Health Research and Testing, Inc., Research Triangle Park, NC. ;Baylor Coll. of Medicine, Houston, TX. Dept. of Pharmacology.
Both mice and rats were injected i.p. with doses of benzo(a)pyrene (B(a)P) ranging from 10 to 100 mg/kg to compare species sensitivity to SCE induction and DNA adduct formation, as well as the relationship between these endpoints. Twenty-four hours after injection, blood was removed by cardiac puncture and the PBLs analyzed for both DNA adduct formation by (32)P-postlabeling and SCE induction following lymphocyte culture. B(a)P induced similar, but not identical, SCE dose-response curves for each species. After B(a)P administration, the major DNA adduct, BPDEI-dGuo, was approximately tenfold more prevalent in the PBLs of the mouse than the rat. If one assumes that BPDEI-dGuo is responsible for the observed SCE induction in each species, then this adduct is a much more efficient SCE inducer in the rat than the mouse. Alternatively, the major adduct may not be causally related to SCE induction. Even though many more adducts are formed in the PBLs of the mouse compared to those of the rat, the rat is the preferred subject for this type of study because of the large amount of blood that can be obtained from each animal as well as the linearity of the dose-response curve for DNA adducts in the PBLs of this species.