Enhanced lung tumor development in tobacco smoke-exposed p53 transgenic and Kras2 heterozygous deficient mice.
A/J mice bearing either a mutation in the p53 gene or a Kras2 heterozygous deficiency were investigated for their susceptibility to tobacco smoke-induced lung tumorigenesis. Transgenic mice and their wild-type littermates were exposed to mainstream tobacco smoke (MS) for 5 mo, followed by 4 mo of recovery in filtered air. In sham (filtered air) groups, p53 transgenic mice did not exhibit a higher tumor multiplicity but did exhibit larger tumors, with tumor load increased 3.6-fold, when compared with wild-type mice. With exposure to MS, tumor multiplicity was increased 60% but there was a strikingly increased tumor load (15.9-fold) in p53 transgenic mice. Increased tumor load (5.3-fold) but not tumor multiplicity was seen in MS-exposed Kras2 heterozygous deficient mice. Interestingly, MS exposure did not increase benzo[a]pyrene-induced lung tumorigenesis when MS exposure was initiated after BaP treatment. These results indicate that a p53 mutation or loss of a Kras2 allele increases susceptibility to MS-induced lung tumor development.
Yan
Ying
Y
Department of Surgery, Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Tan
Qing
Q
Wang
Yian
Y
Wang
Daolong
D
Jin
Mike
M
Gordon
Terry
T
Lubet
Ronald A
RA
You
Ming
M
D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods; D016158:Genes, p53 / Q000235:genetics*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000209:etiology / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000172:deficiency / Q000235:genetics*; D012906:Smoke / Q000009:adverse effects; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D012906:Smoke; D014028:Tobacco Smoke Pollution; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)