Polycyclic aromatic hydrocarbons (PAH) are ubiquitous environmental pollutants that are found in tobacco smoke and residues of fossil fuel combustion. Metabolic activation of intermediate PAH trans-dihydrodiols by aldo-keto reductases (AKRs) results in formation of o-quinones that are electrophilic and redox-active and may contribute to lung cancer. Previously, it was demonstrated that human catechol-O-methyltransferase and sulfotransferases catalyze the Phase II conjugation of PAH-catechols. We investigated whether glucuronidation of PAH-catechols by human UDP-glucuronosyltransferases (UGTs) is able to detoxify benzo[a]pyrene-7,8-dione, a representative PAH o-quinone. RT-PCR showed that human lung adenocarcinoma cells (A549) expressed UGT1A1, 1A3 and 2B7. When B[a]P-7,8-dione (2�M) was incubated with A549 cells for 24 hours, a O-mono-glucuronide conjugate of B[a]P-7,8-catechol was detected in the culture medium by using HPLC-UV and LC-MS/MS. It is concluded that human UGTs may play a critical role in the detoxification of PAH o-quinones [Supported by 1R01-CA-39504,and P30-ES13508 awarded to TMP].

Detoxification of benzo[<i>a</i>]pyrene-7,8-dione by human UDP-glucuronosyltransferases (UGTs)

244th National Meeting (2012)

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Detoxification of benzo[a]pyrene-7,8-dione by human UDP-glucuronosyltransferases (UGTs)