Species differences in the stereochemistry of the metabolism of isoprene in vitro.
1. Comparative studies on the stereochemistry of the metabolism of isoprene in vitro have been carried out using liver microsomes from rats, mice, monkeys, dogs, rabbits and humans. Differences between strains and gender were also investigated. 2. In the production of the isoprene monoepoxides, microsomes from the livers of the male Sprague-Dawley or Wistar rat showed an approximately 2:1 preference for the formation of (S)-2-(1-methylethenyl)oxirane compared with the (R)-enantiomer. No enantioselectivity was observed for mouse or rabbit. In contrast, liver microsomes from dog, monkey or male human preferentially formed (R)-2-(1-methylethenyl)oxirane. There was no enantioselectivity observed with microsomes from female human liver. 3. The significant differences between species in the in vitro metabolism of isoprene indicate that stereochemical and mechanistic data should be taken into account when evaluating the results of animal studies designed to assess the carcinogenic risks to humans that may be associated with exposure to isoprene.
Small
R D
RD
Department of Chemistry, University of Newcastle, UK.
Golding
B T
BT
Watson
W P
WP
D000818:Animals; D002070:Butadienes / Q000737:chemistry* / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004285:Dogs; D004852:Epoxy Compounds / Q000737:chemistry / Q000378:metabolism; D005260:Female; D045782:Hemiterpenes; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology; D010420:Pentanes; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013045:Species Specificity; D013237:Stereoisomerism
D002070:Butadienes; D004852:Epoxy Compounds; D045782:Hemiterpenes; D010420:Pentanes; C005059:isoprene; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D019363:Cytochrome P-450 CYP1A1