Species differences in disposition of benzo[a]pyrene.
Comparison of disposition of benzo[a]pyrene (B[a]P) among Sprague-Dawley rats, Gunn rats, hamsters, and guinea pigs was performed. [3H]B[a]P was administered intratracheally to animals, and the rate of excretion of radioactivity into bile, types of metabolites of B[a]P in bile, and distribution of radioactivity among tissues were determined. In Sprague-Dawley rats, Gunn rats, and guinea pigs, the rate of excretion of radioactivity was dependent upon the administered dose. Excretion and tissue distribution of radioactivity were qualitatively similar among these species although quantitative differences were observed. In hamsters, the rate of excretion was essentially independent of dose at the concentrations examined (0.16 and 350 micrograms). The major difference between hamsters and the other species was that increased amounts of radioactivity were retained in lungs of hamsters at the lower dose with a proportional decrease in the amount of radioactivity excreted into bile. The types and relative amounts of conjugated and nonconjugated metabolites of B[a]P were similar in bile of Sprague-Dawley rats and hamsters. Smaller amounts of glucuronides and larger amounts of sulfate conjugates were detected in bile of Gunn rats than in bile of Sprague-Dawley rats or hamsters. Metabolites in bile of guinea pigs were markedly different from those in the other species in that approximately 90% of the metabolites were thioether conjugates. Buthionine sulfoxime was used to reduce tissue levels of glutathione in Sprague-Dawley rats. When liver and lung glutathione levels were reduced to 30% and 82% of control levels, respectively, the amount of radioactivity excreted into bile was not significantly different from controls.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001564:Benzo(a)pyrene / Q000493:pharmacokinetics*; D001646:Bile / Q000378:metabolism; D019328:Buthionine Sulfoximine; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000493:pharmacokinetics; D006168:Guinea Pigs; D008297:Male; D008647:Mesocricetus; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011911:Rats, Gunn; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014018:Tissue Distribution
D008717:Methionine Sulfoximine; D001564:Benzo(a)pyrene; D019328:Buthionine Sulfoximine; D005978:Glutathione