1,3-Butadiene metabolism by lung airways isolated from mice and rats.
1,3-Butadiene (BD) is oxidized by cytochrome P450 to reactive metabolites, including 1,2-epoxy-3-butene (BMO) and 1,2:3,4-diepoxybutane (BDE), which are thought to be responsible for BD genotoxicity and carcinogenicity. Alveolar-bronchiolar neoplasms were observed in mice but not rats following chronic exposure to BD. The site-specific carcinogenicity of BD in mice may result from metabolic activation in pulmonary tissue. We have incubated bronchioles isolated from both male B6C3F1 mice and male Sprague-Dawley rats with 34 microM BD (final concentration in the aqueous reaction medium) to assess species differences in pulmonary metabolism of BD and to enhance our understanding of species- and site-dependent BD carcinogenicity. Bronchioles from both mice and rats formed BMO, although mouse tissue produced 2-fold more than rat tissue. These preliminary results suggest that pulmonary activation of BD may play a role in the carcinogenicity of BD following inhalation exposure; however, other factors in addition to metabolic differences, probably contribute to the observed differences in susceptibility to BD toxicity.
Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709, USA.
M J
MJ
Seaton
C G
CG
Plopper
J A
JA
Bond
D000818:Animals; D002070:Butadienes / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism*; D004852:Epoxy Compounds / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D002070:Butadienes; D002273:Carcinogens; D004852:Epoxy Compounds; C024370:3,4-epoxy-1-butene; C031763:1,3-butadiene