RGD Reference Report - Quantitative trait loci affecting 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in the rat. - Rat Genome Database

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Quantitative trait loci affecting 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in the rat.

Authors: Tanuma, J  Shisa, H  Iai H, H  Higashi, S  Amada Y, Y  Kamoto, T  Hirayama, Y  Matsuuchi, H  Kitano, M 
Citation: Tanuma J, etal., Cancer Res 1998 Apr 15;58(8):1660-4
RGD ID: 61091
Pubmed: PMID:9563479   (View Abstract at PubMed)

The incidence of tongue carcinomas (TCs) induced by oral administration of 4-nitroquinoline 1-oxide in rats is strain dependent. The inbred Dark-Agouti (DA) strain showed a much higher susceptibility to large mass-forming infiltrative TCs than did the Wistar-Furth (WF) strain. Our previous study (M. Kitano et al, Jpn. J. Cancer Res., 87: 1097-1101, 1996) on crosses between these two strains postulated a dominant susceptibility gene in DA and a dominant resistance gene in WF rats. The present study mapped these loci by analyzing the backcrosses to each parent with simple sequence repeat polymorphisms. Five quantitative parameters were analyzed: (a) the number of TCs > 5 mm in diameter; (b) the total number of TCs per rat; (c) the diameter of the largest TCs (DTCmax values); (d) the number of non-TC cancers per rat; and (e) and the number of cancers of any site per rat. All of these parameters were closely correlated (P < 0.0001). DA rats had a semidominant gene (Stc1) favoring the development of 4-nitroquinoline 1-oxide-induced cancers on chromosome 19, closely linked to D19Mit9. Peak linkage was observed 4 cM distal from D19Mit9, with a logarithm of the odds (lod) score of 5.72 for the number of large TCs and 6.08 for the DTCmax. On the other hand, WF rats had a semidominant gene (Rtc1) mapped between D1Mit1 and D1Mit3, approximately 20 cM from D1Mit1, with a peak lod score of 3.30 for both the number of large TCs and the DTCmax. The main effect of Rtc1 seemed to be to reduce the size of the TCs. The action of these genes was dose dependent and cooperative. The final incidence of TC in DA, WF, F1, and backcross rats seemed to be explained by combinations of genotype at these two loci. Possible candidate genes for Stc1 and Rtc1 are discussed.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
tongue carcinoma inducedIAGP4-nitroquinoline N-oxide61091; 61091 RGD 
Tongue Neoplasms  IDA 61091; 61091 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
decreased tongue tumor incidence  QTM 61091 RGD 
decreased tongue tumor incidence inducedIAGP4-nitroquinoline N-oxide61091compared to treated DA/SlcRGD 
decreased tumor growth/size inducedIAGP4-nitroquinoline N-oxide61091tongue carcinoma and compared to treated DA/SlcRGD 
increased tongue tumor incidence  IDA 61091 RGD 

Objects Annotated

Tcas1  (Tongue tumor susceptibility QTL 1)
Tcat1  (Tongue tumor resistance QTL 1)

DA/Slc  (dark agouti)
WF  (Wistar Furth)

Objects referenced in this article
Marker D19Mit9 D19Mit9 Rattus norvegicus
Marker D1Mit3 D1Mit3 Rattus norvegicus
Marker D1Mit1 D1Mit1 Rattus norvegicus
Strain DA DA Rattus norvegicus
Strain DA.WF-(D1Mgh21-D1Mgh10)(D4Mit11-Nos3)(D1Mit1-D1Mit3)/Kop null Rattus norvegicus
Strain DA.WF-(D1Mgh21-D1Mgh10)(D4Mit11-Nos3)/Kop null Rattus norvegicus
Strain DA.WF-(D1Mit1-D1Mit3)/Kop null Rattus norvegicus
Strain DA.WF-(D4Mit11-Nos3)/Kop null Rattus norvegicus
Gene Nqo1 NAD(P)H quinone dehydrogenase 1 Rattus norvegicus
Gene Stc1 stanniocalcin 1 Rattus norvegicus
Strain WF.DA-(D19Mit1-D19Mit6)/Kop null Rattus norvegicus
Strain WF/Kop null Rattus norvegicus

Additional Information