1,3-BUTADIENE METABOLISM BY LUNG AIRWAYS ISOLATED FROM MICE AND RATS

1,3-Butadiene (ED) is oxidized by cytochrome P450 to reactive metaboli tes, including 1,2-epoxy-3-butene (BMO) and 1,2:3,4-diepoxybutane (BDE ), which are thought to be responsible for ED genotoxicity and carcino genicity. Alveolar-bronchiolar neoplasms were observed in mice but not rats following chronic exposure to ED. The site-specific carcinogenic ity of ED in mice may result from metabolic activation in pulmonary ti ssue. We have incubated bronchioles isolated from both male B6C3F(1) m ice and male Sprague-Dawley rats with 34 mu M BD (final concentration in the aqueous reaction medium) to assess species differences in pulmo nary metabolism of ED and to enhance our understanding of species- and site-dependent ED carcinogenicity. Bronchioles from both mice and rat s formed BMO, although mouse tissue produced 2-fold more than rat tiss ue. These preliminary results suggest that pulmonary activation of ED may play a role in the carcinogenicity of ED following inhalation expo sure; however, other factors in addition to metabolic differences, pro bably contribute to the observed differences in susceptibility to ED t oxicity.