International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

A30. Five Susceptibility QTL to 4-Nitroquinoline 1-Oxide-induced Tongue Cancers in the Rats

Motoo Kitano,1* Jun-ichi Tanuma,1 Masato Hirano,1 Ichiro Semba,1 Akinori Gomi,1 Hayase Shisa2 and Hiroshi Hiai3
1Department of Oral Pathology, Kagoshima University Dental School,
2Laboratory of Basic Cancer Study, Saitama Cancer Center Research Institute and
Department of Pathology and Biology of Diseases, Kyoto University Graduate School of Medicine

Recently, we found that the Dark-Agouti (DA) strain of rats had extremely high susceptibility to 4-nitroquinoline 1-oxide (4NQO)-induced tongue cancers (TC). Virtually 100% of the DA rats given drinking water containing 0.001% 4NQO developed one or more TCs within 180 days of administration, whereas the Wistar/Furth (WF) strain of rats was much less susceptible.

Our previous study of 4NQO treated reciprocal backcross rats mapped a susceptible QTL of DA on rat chromosome (RNO)1 and a resistant QTL of WF on 19, and respectively.

To further scrutinize the genetic predisposition to TC, we analysed 4NQO-induced TCs in 130 (DA x WF) F2 rats with a composite interval mapping. As quantitative parameters, the number of TCs>3mm in diameter (TC#3) and size of the largest TC (TCmax) were used. We found five independent QTL, Tscc1~5 (Tongue squamous cell carcinoma-1~5), with Lod scores for TC#3 of 10.04, 6.85, 4.93, 6.88 and 7.29, which explained phenotypic variance in size and number of TCs in the two strains. Two of these QTL were mapped on RNO1, and the others were mapped on RNO4, 14 and 19, respectively. Judging from the map position, Tscc1 on RNO19 and Tscc2 on RNO1 seemed identical to those found in the previous study, but the other three were novel. We proposed a new nomenclature of QTL consistent with their function. Genome-wide screening of the F2 progeny also suggested the presence of additional three QTL on RNO5, 6 and 10. The susceptibility to TC seemed to be a polygenic trait.

*Address: Motoo Kitano, D.D.S., Ph.D. Department of Oral Pathology, Kagoshima University Dental School, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
Phone 099-275-6140
Fax 099-275-6148

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