Metabolism of 1,3-butadiene to butadiene monoxide in mouse and human bone marrow cells.
1,3-Butadiene (BD), a gas used in the production of rubber and plastics, induces a high incidence of leukemias and lymphomas in B6C3F1 mice. Because of the potential involvement of the hematopoietic system in response to BD, we have examined metabolism of BD by B6C3F1 mouse and human bone marrow and by purified human myeloperoxidase (MPO), an enzyme rich in bone marrow. BD was metabolized to butadiene monoxide (BMO) by MPO and by mouse and human bone marrow cells. In all of these systems metabolism was stimulated by hydrogen peroxide suggesting a peroxidase-mediated process. In B6C3F1 mouse bone marrow cell lysates, hydrogen peroxide but not NADPH stimulated metabolism suggesting that cytochrome P450 was not involved in BMO formation. Metabolism of BD to BMO in hydrogen peroxide-fortified mouse bone marrow cell lysates was more than two orders of magnitude lower than in either NADPH-fortified rat or mouse hepatic microsomes. Experiments using both mouse and human bone marrow cells showed that cells from both sources could generate BMO from BD. These data show that BD can be converted to BMO in a target organ of BD carcinogenicity.
Maniglier-Poulet
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C
Molecular Toxicology and Environmental Health Sciences Program, School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262, USA.
Cheng
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X
Ruth
J A
JA
Ross
D
D
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism*; D001854:Bone Marrow Cells; D002070:Butadienes / Q000378:metabolism*; D002849:Chromatography, Gas; D004852:Epoxy Compounds / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009249:NADP / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002070:Butadienes; D004852:Epoxy Compounds; C024370:3,4-epoxy-1-butene; D009249:NADP; D006861:Hydrogen Peroxide; D009195:Peroxidase; C031763:1,3-butadiene