Five quantitative trait loci affecting 4-nitroquinoline 1-oxide-induced tongue cancer in the rat

In our previous study, Dark-Agouti (DA) rats were found to be highly suscep tible to 4-nitroquinoline 1-oxide (4NQO)-induced tongue carcinoma (TC), whe reas Wistar/Furth (WF) rats were barely susceptible. Interval mapping analy sis of reciprocal backcross rats showed two quantitative trait loci (QTL) o n rat chromosomes (RNO) 1 and 19, In the present study, a composite interva l mapping analysis was applied to 4NQO-induced TC in 130 (DAxWF) F2 rats, d emonstrating five independent QTL, Tongue squamous cell carcinoma 1-5 (Tscc 1-5), responsible for phenotypic differences in the size and number of TCs in the two strains. Two of these QTL were mapped on RNO1, and the others we re mapped on RNO4, 14, and 19. The DA allele at these loci consistently yie lded semidominant susceptibility to TC, Out of the five loci detected in th is F2 generation, Tscc1 and 2 were identical to Stc1 and Rtc1 described in our previous study, but the other three were novel. We propose a new nomenc lature consistent with their function. Genome-nide screening of the F2 prog eny also suggested the presence of three additional QTL on RNO5, 6, and 10, The possible roles of these loci in tongue carcinogenesis are discussed.