Carcinogenesis modifier loci in rat tongue are subject to frequent loss of heterozygosity.
Rats of the DA strain are highly susceptible to 4NQO-induced TCs, whereas WF rats are barely susceptible. In (DA x WF)F2 rats, 5 QTL, Tscc1-5, are responsible for most of the phenotypic variations, though they do not account for all of the phenotypic differences between WF and DA rats. Analysis of 40 tongue tumors >5 mm in diameter from (DA x WF)F1 rats for LOH at the Tscc loci revealed a high frequency of LOH in chromosomal regions where the Tscc2, -3 and -4 loci map. In most cases of LOH, the allele of the barely susceptible WF strain was lost, suggesting that these loci in the WF strain encode tumor-suppressor genes. Analysis of the same tumors for somatic mutations in oncogenes indicated frequent alteration of Ha-ras, which maps in the Tscc3 region, but rare mutation of the p15(INK4B) and p16(INK4A) genes or the p53 and Msh2 genes. Frequent LOH was also found on rat chromosomes 5 (RNO5) and 6 (RNO6). Tumors of large size accumulated LOH at multiple loci, suggesting the involvement of Tscc loci in tumor progression.
Tanuma
Jun-ichi
J
Department of Oral Pathology, Kagoshima University Dental School, Kagoshima, Japan. tanuma@dentb.hal.kagoshima-u.ac.jp
Hiai
Hiroshi
H
Shisa
Hayase
H
Hirano
Masato
M
Semba
Ichiro
I
Nagaoka
Shigetaka
S
Kitano
Motoo
M
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D000818:Animals; D002874:Chromosome Mapping; D005260:Female; D016158:Genes, p53; D011905:Genes, ras; D019656:Loss of Heterozygosity; D008297:Male; D009154:Mutation; D040641:Quantitative Trait Loci; D051381:Rats; D014062:Tongue Neoplasms / Q000139:chemically induced / Q000235:genetics*
D015112:4-Nitroquinoline-1-oxide