Studies on the Mechanism of 1,3-Butadiene-Induced Leukemogenesis: The Potential Role of Endogenous Murine Leukemia Virus

Abstract

Previous studies have revealed marked differences in the incidence of leukemia between rats and mice exposed to 1,3-butadiene that do not appear to be readily explained on the basis of pharmacokinetics or metabolism. Chronic exposure to 1,3-butadiene results in a high incidence of thymic lymphoma in B6C3F1 mice that is not observed in Sprague-Dawley rats. Studies at the Chemical Industry Institute of Toxicology have focused on evaluating the potential of endogenous ecotropic retroviral background to influence susceptibility to 1,3-butadiene leukemogenesis. These studies have compared the pathogenesis and incidence of thymic lymphoma between B6C3F1 and NIH Swiss mice. Proviral ecotropic sequences are truncated in the NIH Swiss mouse, and the virus is not expressed. Chronic exposure to 1,3-butadiene (1250 ppm) for up to 1 year resulted in a fourfold difference in the incidence of thymic lymphoma between B6C3F1 and NIH Swiss mice. These results provide presumptive evidence for retrovirus involvement since NIH Swiss mice lack ecotropic viruses and appear to be relatively resistant to induction of lymphoma by 1,3-butadiene. Other explanations appear to be less likely in light of the fact that target organ toxicity has been determined to be virtually identical between the two strains during the preleukemic phase of 1,3-butadiene exposure.