@article{oai:repo.qst.go.jp:00043220,
 author = {Shimada, Yoshiya and Nishimura, Mayumi and Kakinuma, Shizuko and Ogiu, Toshiaki and Fujimoto, Hirokazu and Kubo, Ayumi and Nagai, Junya and Tano, Keizou and Yoshinaga, Shinji and 島田 義也 and 西村 まゆみ and 柿沼 志津子 and 荻生 俊昭 and 久保 歩 and 永井 絢也 and 吉永 信治},
 journal = {International Journal of Radiation Biology},
 month = {Jun},
 note = {Purpose: Ras activation is one of the major mechanisms for the development
of murine thymic lymphomas by radiation and chemical carcinogens.  To gain
insight into the relationship between genetic susceptibility and ras gene
mutation, the frequency and spectrum of ras gene mutation was examined in
thymic lymphomas from susceptible and resistant mice.
Materials and methods: K- and N-ras mutations in thymic lymphomas that arose
in X-ray-irradiated and N-ethyl-N-nitrosourea (ENU)-treated mice of
susceptible C57BL/6, rather resistant C3H, and their hybrid B6C3F1, were
analyzed by PCR-SSCP and subsequent DNA sequencing.
Results: C57BL/6 exhibited a higher incidence of thymic lymphomas after
exposure to X-rays and ENU than C3H, with B6C3F1 being intermediate. K-ras
gene mutations occurred frequently in the pathogenesis of ENU-induced thymic
lymphomas in susceptible C57BL/6 as opposed to resistant C3H.  The ras
mutations were more frequent in ENU-induced thymic lymphomas than
X-ray-induced thymic lymphomas and with the latter, there was no clear
evidence for strain differences, suggesting that the genetic susceptibility
to X-rays was independent of ras activation. The mutations of K-ras in
thymic lymphomas from C57BL/6 were predominantly GGT-to-GAT in codon 12,
whereas this mutation type was never found in those from C3H.  No strain
difference was observed in the nucleotide sequence or expression levels of
O6-alkylguanine alkyltransferase, indicating that the enzyme did not account
for the genetic susceptibility to ras activation.
Conclusions: The results indicate that there is a clear strain- and
carcinogen-dependency of K-ras mutation, and that the frequency of ras
mutation might determine the genetic susceptibility to ENU-induced
lymphomagenesis, whereas the pathways(s) independent of ras activation might
determine the susceptibility to X-ray-induced lymphomagenesis.},
 pages = {423--430},
 title = {Genetic susceptibility to thymic lymphomas and K-ras gene mutation in mice after exposure to X-rays and N-ethyl-N-nitrosourea},
 volume = {79},
 year = {2003}
}