Benzo[a]pyrene is a procarcinogen produced during
incomplete combustion of organic compounds such as oil, gasoline and charbroiled food.
The mechanism of carcinogenesis of Benzo[a]pyrene is defined
by its enzymatic conversion to the ultimate mutagen, Benzo[a]pyrene diol epoxide
(BPDE,). This molecule intercalates in DNA by forming
covalent bond with the nucleophilic guanine nucleotide bases at the N2 position.
BPDE is the carcinogenic product of three enzymatic
Benzo[a]pyrene is first oxidized by cytochromes P450 to
form a variety of products, including Benzo[a]pyrene
7,8-oxide. The following cytochromes are capable of oxidizing
Benzo[a]pyrene: Cytochrome P450, family 1, subfamily A,
polypeptide 1 (CYP1A1) , ,
Cytochrome P450, family 1, subfamily A, polypeptide 2
(CYP1A2) , , Cytochrome P450,
family 1, subfamily B, polypeptide 1 (CYP1B1) , Cytochrome P450, family 2, subfamily C, polypeptide 18
(CYP2C18) , Cytochrome P450, family 2,
subfamily C, polypeptide 8 (CYP2C8) ,
Cytochrome P450, family 2, subfamily C, polypeptide 9
(CYP2C9) , and Cytochrome P450, family 3,
subfamily A, polypeptide 4 (CYP3A4) .
Benzo[a]pyrene 7,8-oxide is metabolized by Epoxide hydrolase
1, microsomal (xenobiotic) (HYEP) , ,  that opens the epoxide ring to produce
Benzo[a]pyrene-7,8-diol. The ultimate carcinogen is formed
after another reaction with cytochrome P450 to yield the benzopyrene diol epoxide.
The reactive species formed from Benzo[a]pyrene, namely
Benzo[a]pyrene-4,5- 7,8- 9,10- epoxides and others, are substrates for the
conjugation reactions. Conjugation of Benzo[a]pyrene
derivatives is catalyzed by Glutathione S-transferase pi 1
(GSTP1) , , UDP
glucuronosyltransferase 1 family, polypeptide A10 (UGT1A10)
, UDP glucuronosyltransferase 1 family, polypeptide A6
(UGT1A6) , ,
UDP glucuronosyltransferase 1 family, polypeptide A7C
(UGT1A7C) , UDP
glucuronosyltransferase 1 family, polypeptide A9
(UGT1A9) , .
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