Formation and repair of DNA lesions in the p53 gene: Relation to cancer mutations?

✍ Scribed by Gerd P. Pfeifer; Mikhail F. Denissenko

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 137 KB
• Volume: 31
• Category: Article
• ISSN: 0893-6692
• DOI: 10.1002/(sici)1098-2280(1998)31:3<197::aid-em1>3.0.co;2-i

✦ Synopsis

The number and diversity of mutations in the p53 muta-smoke component benzo [a]pyrene representing the tion data base provides indirect evidence that impli-polycyclic aromatic hydrocarbon class of carcinogens. cates environmental mutagens in human carcinogene-The damage/repair data obtained for these mutagens sis. The p53 gene has a large mutational target size; can predict certain parameters of the mutational specmore than 280 out of 393 amino acids are found tra including the distribution of hotspots in human nonmutated in tumors. We argue that there is possibly a melanoma skin cancers and lung cancers from smoklimited involvement of selection for specific mutations ers. Future studies with suspected mutagens may help in the central domain of the protein, and that the distri-to implicate causative agents involved in other canbution of DNA damage along the p53 gene caused cers, such as colon and breast cancer, where the exact by environmental carcinogens can be correlated with carcinogen has not yet been identified but an environthe mutational spectra, i.e., hotspots and types of muta-mental factor is suspected. Environ. Mol. Mutagen. tions, of certain cancers. This concept has been vali-31:197-205, 1998