Absence of detectable P450 2E1 in bone marrow of B6C3F1 mice: relevance to butadiene-induced bone marrow toxicity.
The observation that the concentration of butadiene monoepoxide (BMO) is greater in bone marrow than in the blood following inhalation of 1,3-butadiene (BD) by B6C3F1 mice prompted the present investigation into whether cytochrome P450 2E1, the isozyme believed to be involved in the epoxidation of BD, is present in the bone marrow of B6C3F1 mice. The bone marrow of male and female B6C3F1 mice was analyzed by Western blot analysis and immunohistochemistry to determine whether cytochrome P450 2E1 is present, and, if present, in which cell types. Both Western blot and immunohistochemical analyses revealed the apparent absence of P450 2E1 in B6C3F1 mouse bone marrow. This observation suggests that BD is converted to BMO outside of bone marrow and is subsequently concentrated in the bone marrow, or that the conversion of BD to BMO occurs by an alternate enzymatic pathway within the bone marrow.
Genter
M B
MB
Department of Toxicology, North Carolina State University, Raleigh 27695.
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D000818:Animals; D015153:Blotting, Western; D001853:Bone Marrow / Q000201:enzymology*; D001855:Bone Marrow Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D002070:Butadienes / Q000493:pharmacokinetics / Q000633:toxicity*; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000378:metabolism*; D004852:Epoxy Compounds / Q000493:pharmacokinetics; D005260:Female; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009153:Mutagens / Q000493:pharmacokinetics; D010089:Oxidoreductases, N-Demethylating / Q000032:analysis / Q000378:metabolism*
D002070:Butadienes; D004852:Epoxy Compounds; D007202:Indicators and Reagents; D009153:Mutagens; C024370:3,4-epoxy-1-butene; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating