A speed congenic rat strain bearing the tongue cancer susceptibility locus Tscc1 from Dark-Agouti rats.
We previously reported that Dark-Agouti (DA) rats are highly susceptible to 4-nitroquinoline 1-oxide (4NQO)-induced tongue cancer (TC), whereas Wistar/Furth (WF) rats are barely susceptible. Linkage analysis of reciprocal (DAxWF)F2 rats demonstrated five quantitative trait loci, 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 WF.DA-Tscc1 (WF-T1D) rats, i.e. WF rats carrying a DA-derived Tscc1 chromosomal segment, and 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, indicating that the introgressed segment contains one of the susceptibility loci for 4NQO-induced TCs from DA rats. Detection of a single nucleotide polymorphism in NQO1, one of the Tscc1 candidate genes, enabled us to map NQO1 in the Tscc1 segment between D19Wox8 and D19Wox7 on chromosome 19. Possible relevance of NQO1 polymorphism to TC susceptibility is discussed.
Hirano
Masato
M
Department of Oral Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan. hirano@denta.hal.kagoshima-u.ac.jp
Tanuma
Jun-Ichi
J
Hirayama
Yoshikazu
Y
Ohyama
Masanobu
M
Semba
Ichiro
I
Wakusawa
Shinya
S
Shisa
Hayase
H
Hiai
Hiroshi
H
Kitano
Motoo
M
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics*; D002875:Chromosomes / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D007178:Inbreeding; D015994:Incidence; D008297:Male; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D051381:Rats; D011920:Rats, Inbred WF; D014062:Tongue Neoplasms / Q000139:chemically induced / Q000235:genetics*
D002273:Carcinogens; D015112:4-Nitroquinoline-1-oxide