The metabolism of nonane, a JP-8 jet fuel component, by human liver microsomes, P450 isoforms and alcohol dehydrogenase and inhibition of human P450 isoforms by JP-8.
Nonane, a component of jet-propulsion fuel 8 (JP-8), is metabolized to 2-nonanol and 2-nonanone by pooled human liver microsomes (pHLM). Cytochrome P450 (CYP) isoforms 1A2, 2B6 and 2E1 metabolize nonane to 2-nonanol, whereas alcohol dehydrogenase, CYPs 2B6 and 2E1 metabolize 2-nonanol to 2-nonanone. Nonane and 2-nonanol showed no significant effect on the metabolism of testosterone, estradiol or N,N-diethyl-m-toluamide (DEET), but did inhibit carbaryl metabolism. JP-8 showed modest inhibition of testosterone, estradiol and carbaryl metabolism, but had a more significant effect on the metabolism of DEET. JP-8 was shown to inhibit CYPs 1A2 and 2B6 mediated metabolism of DEET, suggesting that at least some of the components of JP-8 might be metabolized by CYPs 1A2and/or 2B6.
Edwards
Jeffrey E
JE
Environmental and Molecular Toxicology, North Carolina State University, Box 7633, Raleigh, NC 27695, USA.
Rose
Randy L
RL
Hodgson
Ernest
E
D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003671:DEET / Q000493:pharmacokinetics; D004958:Estradiol / Q000378:metabolism; D005579:Fossil Fuels; D006801:Humans; D006838:Hydrocarbons / Q000493:pharmacokinetics* / Q000633:toxicity*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D013739:Testosterone / Q000378:metabolism
D065607:Cytochrome P-450 Enzyme Inhibitors; D005579:Fossil Fuels; D006838:Hydrocarbons; D007527:Isoenzymes; C098607:JP8 aviation fuel; D003671:DEET; D013739:Testosterone; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; D000426:Alcohol Dehydrogenase