Effects of 1-ethynylpyrene and related inhibitors of P450 isozymes upon benzo[a]pyrene metabolism by liver microsomes.
The effects of three aryl acetylenes, 1-ethynylpyrene (EP), 2-ethynylnaphthalene (EN) and 3-ethynylperylene (EPE), upon the metabolism of benzo[a]pyrene (BaP) by microsomes isolated from rat liver were investigated. These aryl acetylenes all inhibited the total metabolism of BaP. Formation of BaP 7,8-dihydrodiol and BaP tetrol products by microsomal preparations from rats that had been pretreated with 3-methylcholanthrene (3MC) were preferentially inhibited. The effects of EP upon the metabolism of BaP 7,8-dihydrodiol by microsomes from rat liver were also studied. This aryl acetylene strongly inhibited the formation of BaP tetrols from BaP 7,8-dihydrodiol by liver microsomes both from untreated rats and from rats pretreated with 3MC, but enhanced the conversion of the BaP dihydrodiol into other metabolites.
Hall
M
M
Chester Beatty Laboratories, Institute of Cancer Research, Royal Cancer Hospital, London, U.K.
Parker
D K
DK
Grover
P L
PL
Lu
J Y
JY
Hopkins
N E
NE
Alworth
W L
WL
D000818:Animals; D001564:Benzo(a)pyrene / Q000737:chemistry / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D008748:Methylcholanthrene; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology*; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D011721:Pyrenes / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D065607:Cytochrome P-450 Enzyme Inhibitors; D007527:Isoenzymes; D009281:Naphthalenes; D011721:Pyrenes; C066331:3-ethynylperylene; C065012:2-ethynylnaphthalene; D001564:Benzo(a)pyrene; C042881:1-ethynylpyrene; D008748:Methylcholanthrene; D010569:Perylene