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Stephen S. Hecht, Metabolically Activated Carcinogens and Mutations in the p53 Tumor Suppressor Gene in Lung Cancer, JNCI: Journal of the National Cancer Institute, Volume 92, Issue 10, 17 May 2000, Pages 782–783, https://doi.org/10.1093/jnci/92.10.782
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The article by Smith et al. (1) in this issue of the Journal extends the elegant work of this group on mapping reaction sites of polycyclic aromatic hydrocarbon (PAH) diol epoxides and other activated carcinogens in the p53 tumor suppressor gene (also known as TP53) (2–4). Previously, these investigators (4) have shown that diol epoxides of benzo[a]pyrene (B[a]PDE) and benzo[g]chrysene, as well as N-acetoxy-2-acetylaminofluorene and aflatoxin B1 8,9-epoxide, preferentially bind at methylated CpG sequences in the p53 gene. In the present study (1), they mapped the distribution of adducts induced by diol epoxides of five PAH compounds—5-methylchrysene, 6-methylchrysene, chrysene, benzo[g]chrysene, and benzo[c]phenanthrene—in the nontranscribed strand of p53 in normal human bronchial epithelial cells. The results were consistent with those of their previous studies, in that CpG sequences were commonly adducted (2,4). Moreover, the distribution of adducts corresponded closely to the sites of highest mutation frequency in the p53 gene in lung cancers from smokers, but it was substantially different from that in lung cancers from nonsmokers. These results provide further support for the critical role of metabolically activated cigarette smoke carcinogens as the cause of lung cancer in smokers (5).