Dark-Agouti系ラット由来の舌がん感受性QTLをWistar-Furth系ラットにスピードコンジェニック法で導入して樹立したWF-T1D系ラット

概要

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Previously we reported that Dark-Agouti (DA) rat strain is highly susceptible to 4-nitroquinoline 1-oxide (4NQO)-induced tongue cancer (TC), whereas Wistar-Furth (WF) rat strain is resistant. Linkage analysis of reciprocal (DAxWF) F2 rats demontstrated five quantitative trait loci (QTLs), named 'Tongue squamous cell carcinoma 1-5 (Tscc1-5)', determining the size and number of the TCs. The major susceptibility locus Tscc1 is mapped on rat chromosome 19. In the present study, we used a marker-assisted speed congenic procedure to construct a special congenic strain of rats, i.e., WF rats carrying a DA-derived Tscc1 chromosomal segment between D19Wox8 and D19Wox7 on chromosome 19. We, now, call it 'WF.DA-Tscc1 (WF-T1D) strain of rats'. Using this newly established rat strain we evaluated the effect of a single Tscc1 on 4NQO-induced tongue carcinogenesis. In WF-T1D rats the incidence, number and size of 4NQO-induced TCs were significantly higher than those in WF rats. It is appropriate to consider that the introgressed segment contains one of the susceptibility loci for 4NQO-induced TCs in the rats. Otherwise, we found out a single nucleotide-polymorphism between the DA and WF rats in NQO1, which is one of the candidate genes of Tscc1, and subsequently we mapped NQO1 in the Tscc1 segment on chromosome 19. NQO1-polymorphism should be considered possible relevance to TC susceptibility.
2006-03-20