Benzo[a]pyrene-7,8-dihydrodiol Promotes Checkpoint Activation and G2/M Arrest in Human Bronchoalveolar

Polycyclic aromatic hydrocarbons (PAHs) are potent carcino-gens that require metabolic activation inside cells. The proxi-mate carcinogens PAH-diols can be converted to o-quinones by aldo-keto reductases (AKRs) or to diol-epoxides by cyto-chrome P450 (P450) enzymes. We assessed the effect of ben-zo[a]pyrene-7,8-dihydrodiol (BPD) on proliferation in p53-null bronchoalveolar carcinoma H358 cells. BPD treatment led to a significant inhibition of proliferation and arrest in G2/M in H358 cells. The relative contribution of the AKR and P450 pathways to cell cycle arrest was assessed. Overexpression of AKR1A1 did not affect cell proliferation or cell cycle progression, and benzo[a]pyrene-7,8-dione did not cause any noticeable effect on cell growth, suggesting that AKR1A1 metabolic products were not involved in the antiproliferative effect of BPD. On th