HIGH-CONCENTRATIONS OF BUTADIENE EPOXIDES IN LIVERS AND LUNGS OF MICECOMPARED TO RATS EXPOSED TO 1,3-BUTADIENE

1,3-Butadiene (BD) is carcinogenic in B6C3F1 mice and Sprague-Dawley r ats, and mice are more sensitive than rats. This study measured the co ncentrations of the putative DNA-reactive BD metabolites, butadiene mo noxide (BMO) and butadiene diepoxide (BDE), in lung and liver of male Sprague-Dawley rats and B6C3F1 mice exposed to BD by inhalation. Sampl es (n = 3-6) of lung and liver were collected at 3 and 6 hr during and at 6 and 12 min following 6-hr nose-only inhalation exposure to 0, 62 .5, 625, 1250, or 8000 (rats only) ppm BD. BMO and BDE were extracted into methylene chloride and quantified by gas chromatography-mass spec trometry. Since BD epoxides can be conjugated with glutathione (GSH), the nonprotein sulfhydryl content of lung and liver was quantified col orimetrically. Analytical limitations precluded quantitation of BD epo xides in tissues of rats or mice exposed to 62.5 ppm BD. Exposures gre ater than or equal to 625 ppm BD resulted in higher BMO concentrations in lungs and livers of mice compared to rats. In mice exposed to 625 and 1250 ppm BD, the maximum concentrations of BMO at 3 or 6 hr of exp osure in lungs (2.6 +/- 0.2 and 3.7 +/- 1.2 nmol/g tissue; mean +/- SE ) were higher than in livers (0.58 +/- 0.12 and 0.93 +/- 0.19 nmol/g). Rats exposed to 625 and 1250 ppm BD had lower concentrations of BMO i n lungs (0.16 +/- 0.03 and 0.31 +/- 0.07 nmol/g) and livers (0.06 +/- 0.01 and 0.16 +/- 0.06 nmol/g) than mice. In rats exposed to 8000 ppm BD, the maximum concentrations of BMO in lungs (1.3 +/- 0.2 nmol/g) an d livers (1.2 +/- 0.1 nmol/g) were nearly identical. BDE was quantifie d in lungs, but not livers, of mice exposed to 625 and 1250 ppm BD. Th e maximum concentrations of BDE in mouse lungs were 0.71 +/- 0.06 and 1.5 +/- 0.1 nmol/g, respectively; BDE was not detected in livers or lu ngs of rats exposed to any of the concentrations of BD tested. GSH dep letion was dependent on the concentration and duration of BD exposure. The lungs of mice sustained the greatest magnitude of depletion (26% of control at 6 hr of exposure to 1250 ppm BD). The data from these st udies suggest that GSH depletion is associated with BD epoxide tissue concentrations in vivo and that the greater sensitivity of mice to BD- induced carcinogenicity can be explained, in part, by the higher level s of both BMO in lungs and livers and BDE in the lungs of mice compare d to rats. (C) 1995 Academic Press, Inc.