Characteristic association between K-ras gene mutation with loss of heterozygosity in X-ray-induced thymic lymphomas of the B6C3F1 mouse.
OBJECTIVE
To elucidate the characteristics of radiation carcinogenesis, the spectra of K- and N-ras oncogene mutations, loss of heterozygosity (LOH) and their association in X-ray-induced thymic lymphomas (TL) were determined by comparing with those of N-ethyl-N-nitrosourea (ENU)-induced and spontaneously occurring TL.


METHODS
TL that arose in untreated, X-ray-irradiated and ENU-treated B6C3F1 mice were examined both for K- and N-ras mutations by PCR-SSCP and DNA sequencing and for LOH by PCR with polymorphic microsatellite markers.


RESULTS
(1) ras gene mutations were found in a proportion of TL from X-ray-exposed (approximately 20%) and ENU-treated (30-40%) mice while no ras gene mutations were found in spontaneous TL. N-ras mutations were rare. (2) The spectrum of ras gene mutations was diverse and seemed to differ little between X-ray-induced and ENU-induced TL, even though there was a higher frequency of ras mutations in ENU-induced TL that clustered to K-ras codon 12. (3) The X-ray-induced TL showing K-ras mutation were associated with LOH on chromosome 6, while those showing no K-ras mutation were associated with high frequency of LOH on chromosomes 4, 11 and 12.


CONCLUSIONS
These results demonstrate that, in the B6C3F1 mouse TL, X-ray-induced lymphomagenesis showed both the co-expression, yet low occurrence of allelic imbalance on chromosome 6 and K-ras mutation, and exclusive expression of frequent allelic imbalance on chromosomes 4, 11 and 12 and K-ras mutation.
Shimada
Y
Y
Low Dose Radiation Risk and Carcinogenesis Research Group, National Institute of Radiological Sciences, Chiba, Japan. y_shimad@nirs.go.jp
Nishimura
M
M
Kakinuma
S
S
Takeuchi
T
T
Ogiu
T
T
Suzuki
G
G
Nakata
Y
Y
Sasanuma
S
S
Mita
K
K
Sado
T
T
D000818:Animals; D005038:Ethylnitrosourea; D005260:Female; D011905:Genes, ras; D019656:Loss of Heterozygosity; D008223:Lymphoma / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009154:Mutation; D013953:Thymus Neoplasms / Q000235:genetics*; D014965:X-Rays
D005038:Ethylnitrosourea