The oxidation of benzo[a]pyrene (B[a]P) was examined using reconstitut
ed systems prepared with recombinant human cytochrome P450 (P450) enzy
mes 1A1, 1A2, 2C8, 2C10, 2E1, and 3A4 and with microsomes prepared fro
m Saccharomyces cerevisiae expressing recombinant human P450s 2C8, 2C9
, and 2C18. Products measured by HPLC included the 3- and 9-phenols, t
he 4,5-, 7,8-, and 9,10-dihydrodiols (detected in the presence of epox
ide hydrolase), and products in the polar fraction eluting immediately
after the void volume. The most active enzyme in all reactions was P4
50 1A1. P450 3A4 and P450 1A2 formed appreciable amounts of several of
the products, including the 3-phenol. P450 2C enzymes and P450 2E1 fo
rmed relatively low amounts of all B[a]P products. Consideration of th
ese patterns along with knowledge of levels of expression of the P450s
in human tissues and previous results with microsomes leads to the co
nclusion that P450 1A1 should dominate the oxidation of B[a]P in tissu
es where it is present and inducible. In human liver the level of P450
1A1 is low and P450 3A4, P450 2C subfamily enzymes, and P450 1A2 prob
ably all contribute. Of the human P450s considered here, P450 1A2 was
the most active hepatic enzyme forming the 7,8-dihydrodiol. 7,8-Benzof
lavone stimulated the oxidation of B[a]P by P450 3A4 and inhibited the
oxidations catalyzed by P450 1A2. The extent of inhibition of P450 1A
1 was less (than with P450 1A2), probably due to the rapid oxidation o
f 7,8-benzoflavone by P450 1A1. The major 7,8-benzoflavone product app
ears to be the 5,6-oxide.