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© 1992 Oxford University Press

research-article

Comparison of Ki-ras gene mutation among simultaneously occurring multiple urethan-induced lung tumors in individual mice

Hisamitsu Ohmori 1 2, Tetsuya Abe 1, Hideyasu Hirano 1, Tadamasa Murakami 1, Takahiko Katoh 1, Sadao Gotoh 1, Masamitsu Kido 2, Akio Kuroiwa 3, Taisei Nomura 4 and Ken Higashi 1 5

1Department of Biochemistry
2Division of Respiratory Disease
3Second Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health Kitakyushu 807
4Department of Radiation Biology, Osaka University Medical School Suita, Osaka 565, Japan

5To whom correspondence should be addressed

Mouse lung tumors were induced in C57BL/6J(female) × A/J(male) F1 mice by a single s.c. injection of urethan. About 6 months later, multiple small-sized lung tumors were detectable in almost all mice. After a further 6 months, some of these tumors became larger than the rest. We examined whether there were any mutational differences among multiple lung tumors in a single mouse. Direct DNA sequencing of a separately amplified Ki-ras gene by polymerase chain reaction (PCR) was carried out with 25 DNA samples from multiple tumors in four mice. Twenty-four of 25 tumors (96%) had mutations at the codon 61 of the Ki-ras gene. The major mutations involved were either AT to GC transition (44%) or AT to TA transversion (44%) at the second base of codon 61. We compared the types of these gene mutations among the tumors from each of two mice from two different groups of siblings and then compared the two groups. Interestingly, in the first group of siblings, we detected CTA in 5/6 tumors in the first mouse and again CTA in 4/6 tumors in the second one. In the second group of siblings, we detected CGA in 5/7 tumors in one mouse and CGA again in 3/5 tumors in the second mouse. These results show that the pattern of Ki-ras codon 61 mutations in urethan-induced lung tumors is similar in tumors developing in siblings, suggesting that host factors have an effect on the carcinogen-induced mutational pattern. There was no major mutational difference between small and large tumors. The results suggested that other event(s) in addition to the mutation of the Ki-ras gene might play a role during the development of large-sized tumors.


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