OXIDATION OF 1,3-BUTADIENE TO (R)-BUTADIENE AND (S)-BUTADIENE MONOXIDE BY PURIFIED RECOMBINANT CYTOCHROME P4502E1 FROM RABBIT, RAT AND HUMAN

1,3-Butadiene (BD) is a gas used widely in the rubber and plastics ind ustry as an intermediate in production processes and has been detected in automobile exhaust and cigarette smoke. ED requires metabolic acti vation to exert toxicity and has been shown to be carcinogenic in rode nts. IARC has classified ED as a group 2A (probably carcinogenic to hu mans) carcinogen. The initial oxidation of ED to butadiene monoxide (B MO) occurs primarily via cytochrome P450 2E1 and two stereoisomers of BMO (R and S) can be formed. (R) and (S)-BMO are metabolized different ly and demonstrate markedly different toxicities in isolated rat hepat ocytes. This work examined the generation of (Ii) and (S)-BMO from ED by cytochrome P450 2E1 from rabbit, rat and human. BMO level was measu red by GC-MS analysis and enantiomeric composition was determined by G C-FID. The greatest rate of formation of BMO from ED was obtained with rabbit cytochrome P4502E1 followed by human and then by rat. Enantiom eric distribution of R and S-BMO produced by the three species demonst rated no significant differences. (C) 1998 Elsevier Science Ireland Lt d. All rights reserved.