Maps of susceptible and/or resistant genes to chemically induced tongue carcinomas using the rat derived from a speed congenic strain originating from the Dark-Agouti and Wistar/Furth progenitors

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We have recently reported that the susceptibility of rats to tongue cancers (TCs) induced by 4-nitroquinoline 1-oxide (4NQO) substantially varies depending on the genetic background of organisms. In present study, to map NQO1 encoding the catalytic enzyme of 4NQO, we have investigated DNA sequence analysis of NQO1 in rats for detecting polymorphisms of NQO1. As a result, we have found genetic difference of NQO1 between DA and WF strains. This genetic difference has characterized single nucleotide polymorphisms (SNPs) which shows a C in DA rat and a T in WF rat at nucleotide position 121, which exists in the 5'-flanking region of NQO1 structural gene. Furthermore, by PCR-RFLP analysis utilizing this SNPs, we also have found that NQO1 in rats locates on about 17-cM between D19Rat15 and D19Rat90 on Chr 19. In addition, we also have revealed that DNA sequence at intron 3 of NQO1 is 280-bp longer in DA and WF strains than that of NQO1 known generally. Our study may make it possible to pinpoint the candidate genes for particular diseases, and play an important role in throwing light on the mechanism not only of the experiments of the rat models, but also human diseases, by referring to the syntenic regions of the mouse and human chromosomes.