Benzo[a]pyrene-induced murine skin tumors exhibit frequent and characteristic G to T mutations in the p53 gene.

摘要: Human tobacco-related cancers exhibit a high frequency of G to T transversions in the mutation hot spot region p53 tumor suppressor gene, possibly result specific mutagens tobacco smoke, most notably benzo[a]pyrene (B[a]P). No vivo animal model B[a]P-induced tumorigenesis has been used, however, substantiate these molecular epidemiological data experimentally. Direct DNA sequence analysis (exons 5-8 inclusive) murine was performed 20 skin tumors induced by complete carcinogenesis protocol with B[a]P. Sequence analyses revealed numerous heterozygous missense mutations carcinomas, specifically exons 7 and 8 targeting exclusively guanine residues. Moreover, 70% (5/7) characterized were transversions. In contrast, direct 36 7,12-dimethylbenz[a]anthracene (DMBA) either or two-stage 30% mutations, majority found but only single transversion (1/8). Thus, while frequencies are similar, pattern type differs significantly from spectra DMBA-induced squamous neoplasias. These findings lend support vitro evidence, suggesting that gene may be selective target metabolically activated B[a]P species etiologically associated human cancers.