Susceptibilities of p53 knockout and rasH2 transgenic mice to urethane-induced lung carcinogenesis are inherited from their original strains.
In the present study, susceptibility of CB6F1 mice carrying the human prototype c-Ha-ras gene (rasH2 mice) and p53 gene knockout mice (p53 (+/-) mice) to urethane-induced lung carcinogenesis was compared under the same experimental conditions. Both strains were administered 500 ppm urethane in their drinking water for 3 weeks. At week 26, lung adenocarcinomas and adenomas were observed in 53% and 100% of rasH2 mice, respectively, and lung adenomas were observed in 67% of rasH2 littermate (non-Tg) mice. However, lung tumors were not observed in either p53 (+/-) or p53 (+/+) mice. Peliosis hepatis and hepatic hemangiomas were observed in 27% and 67% of p53 (+/-) mice, but only in 6.7% and 6.7% of the rasH2 animals, respectively. Under the same experimental conditions, BALB/c mice, the strain of origin of the rasH2 mice, developed lung adenomas at an incidence of 93%, whereas none of the C57BL/6 original strain for p53 (+/-) mice developed lung tumors. Peliosis hepatis was observed in 40% of the C57BL/6 mice, but not in BALB/c mice; hepatic and splenic hemangiomas were not observed in these animals. These results indicate that organ susceptibility of rasH2 and p53 (+/-) mice is inherited from their strains of origin, the rasH2 and BALB/c lines being much more sensitive to the induction of pulmonary carcinogenesis.
Ozaki
Masakazu
M
Department of Experimental Pathology and Tumor Biology, Nagoya City University, Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan. ozakim@sc.sumitomochem.co.jp
Ozaki
Keisuke
K
Watanabe
Tomoyuki
T
Uwagawa
Satoshi
S
Okuno
Yasuyoshi
Y
Shirai
Tomoyuki
T
D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D000236:Adenoma / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D016158:Genes, p53; D011905:Genes, ras; D020022:Genetic Predisposition to Disease; D006965:Hyperplasia / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014520:Urethane / Q000633:toxicity
D014520:Urethane