6533b7dbfe1ef96bd1270ad2
RESEARCH PRODUCT
Biological activation of 1,3-butadiene to vinyl oxirane by rat liver microsomes and expiration of the reactive metabolite by exposed rats.
J.g. FilserH P RolzhäuserK LieserH M BoltG. SchmiedelVolker SchurigDorothee Wistubasubject
MaleCancer ResearchCytochromeMetaboliteEpoxideIn Vitro TechniquesAcetonechemistry.chemical_compoundEthers CyclicmedicineButadienesAnimalsBiotransformationbiology13-ButadieneRats Inbred StrainsStereoisomerismGeneral MedicineGlutathioneMetabolismRatsOncologychemistryBiochemistryMicrosomebiology.proteinMicrosomes LiverEpoxy CompoundsPhenobarbitalmedicine.drugMutagensdescription
When 1,3-butadiene is incubated with rat liver microsomes and NADPH both enantiomers of vinyl oxirane are formed, the amount of epoxide being dependent on incubation time, microsomal protein, and substrate concentration. Inhibition by SKF 525 A or dithiocarb as well as induction by pretreatment with phenobarbital or 20-methylcholanthrene suggest participation of cytochrome P-450 in this reaction. The amount of epoxide is enhanced by addition of 1,1,1-trichloropropene oxide and reduced by glutathione, especially in the presence of hepatic cytosol. When rats are exposed to 1,3-butadiene in a closed chamber (conditions of maximal metabolism) vinyl oxirane is exhaled and can be quantitatively determined from the gas phase. The concurrent exhalation of acetone is consistent with the idea of biologic action of a reactive metabolite.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1983-10-01 | Journal of cancer research and clinical oncology |