On the origin of G --> T transversions in lung cancer.
G-->T transversions in the TP53 gene are more common in lung cancers from smokers than in any other cancer except for hepatocellular carcinomas linked to aflatoxin. The high frequency of G-->T transversions in lung cancer has been attributed to the mutagenic action of cigarette smoke components, in particular polycyclic aromatic hydrocarbons (PAH). In a recent review [Mutat. Res. 508 (2002) 1-19], Rodin and Rodin have questioned the direct mutagenic action of PAH-like compounds and have suggested that other factors, such as selection of pre-existing endogenous mutations by smoke-induced stress, can better explain the excess of G-->T transversions in lung tumors. Their two main arguments against an involvement of PAH are that smoking may inhibit the repair of G-->T primary lesions on the non-transcribed strand and that lung cancer cell lines show a higher frequency of G-->T transversions than primary lung tumors suggesting that these mutations are not related to smoking. We illustrate here that both of these suggestions are incompatible with available evidence and that the abundance and sequence specificity of G-->T transversions in lung tumors is best explained by a direct mutagenic action of PAH compounds present in cigarette smoke.
Pfeifer
Gerd P
GP
Department of Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA. gpfeifer@coh.org
Hainaut
Pierre
P
D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D004273:DNA, Neoplasm / Q000187:drug effects*; D030541:Databases, Genetic; D005787:Gene Frequency; D006147:Guanine / Q000737:chemistry; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D016296:Mutagenesis / Q000187:drug effects; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D013936:Thymidine / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D004273:DNA, Neoplasm; D011084:Polycyclic Aromatic Hydrocarbons; D016159:Tumor Suppressor Protein p53; D006147:Guanine; D013936:Thymidine