Journal Article

Metabolic activation of the potent carcinogen dibenzo[<i>a, l</i>]pyrene by human recombinant cytochromes P450, lung and liver microsomes

Magang Shou, Kristopher W. Krausz, Frank J. Gonzalez and Harry V. Gelboin

in Carcinogenesis

Volume 17, issue 11, pages 2429-2433
Published in print November 1996 | ISSN: 0143-3334
Published online November 1996 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.11.2429
Metabolic activation of the potent carcinogen dibenzo[a,
                        l]pyrene by human recombinant cytochromes P450, lung and liver
                    microsomes

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The metabolic activation of dibenzo[a, l]pyrene (DB[a, l]P), recently considered the most potent carcinogen among all polycyclic aromatic hydrocarbons, to the 11, 12-dihydrodiol, a precursor of the ultimate carcinogens, the 11, 12-diol-13, 14-epoxides, was investigated using eleven human recombinant cytochrome P450s, as well as human lung and liver microsomes. Of all human P450s, 1A1 was the most active in the metabolism of DB[a, l]P (310 pmol/min, nmol P450) and had 5–23-fold higher catalytic activity than other P450s examined. The order of activity in the formation of the 11, 12-dihydrodiol was as follows: 1A1 (116 pmol/min, nmol P450) > 2C9 (29) > 1A2 (22) > 2B6 (18) > 3A4 (16) > others (≤ 5). The Km of 1A1 for DB[a, l]P and Vmax for the formation of 11, 12-dihydrodiol were 3.9 μM and 0.13/ min, respectively. Liver microsomes from 14 individuals were shown to metabolize DB[a, l]P and the rates for production of 11, 12-dihydrodiol ranged from 4 to 71 pmol/ min, nmol P450. Lung microsomes from six organ donors formed the 11, 12-dihydrodiol at a rate from 0.1 to 13 pmol/ min, mg of microsomal protein. These findings describe the potential of individual P450s present in liver and lung to contribute to the metabolic activation and the carcino-genicity of DB[a, l]P.

Journal Article.  0 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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