Tobacco smoke-induced lung tumorigenesis in mutant A/J mice with alterations in K-ras, p53, or Ink4a/Arf.

摘要: A/J mice with genetic alterations in K-ras, p53, or Ink4a/Arf were employed to investigate whether carrying these germline mutations would be susceptible tobacco smoke-induced lung tumorigenesis. Transgenic of both genders and their wild-type littermates exposed environmental cigarette smoke for 6 months, followed by recovery air 5 months. A significant increase tumor multiplicity was observed mutant when compared mice. Furthermore, an additive effect between the a p53 transgene Ink4A/Arf deletion during Sequence analysis K-ras gene indicated that had occurred at either codon 12/13 61 spontaneously occurring (air control) tumors. found 62% tumors from air-control animals 83% those smoke. The mutation spectrum is somewhat similar In addition, we identified three novel 12: GGT (Gly) --> TTT (Phe), ATT (Ile), CTT (Leu). These findings provide evidence play role smoke-related carcinogenesis. similarity spectra oncogene tumors, as spontaneous suggests enhances tumorigenesis primarily through promoting mutations.