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Chromosome mapping of multiple loci affecting the genetic predisposition to rat liver carcinogenesis

De Miglio, Maria Rosaria and Pascale, Rosa Maria and Simile, Maria Maddalena and Muroni, Maria Rosaria and Calvisi, Diego Francesco and Virdis, Patrizia and Bosinco, Giovanni M. and Frau, Maddalena and Seddaiu, Maria Antonietta and Ladu, Sara and Feo, Francesco (2002) Chromosome mapping of multiple loci affecting the genetic predisposition to rat liver carcinogenesis. Cancer Research, Vol. 62 (15), p. 4459-4463. eISSN 0008-5472. Article.

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Abstract

Previous studies on (BNxF344)F1 (BFF1) rat model of genetic predisposition to hepatocarcinogenesisled to the identification, in BFF1xF344 backcross progeny, of two hepatocarcinogenesis susceptibility (Hcs) and three resistance (Hcr) loci affecting the progression of neoplastic liver nodules. To evaluate the presence of other hepatocarcinogenesis-related loci in the BFF1 genome, nodule induction by resistant hepatocyte model in 116 male BFF2 rats 32 weeks after initiation with diethylnitrosamine was subjected to quantitative trait loci analysis. The rats were typed with 179 genetic markers, and linkage analysis identified three loci on chromosomes 1, 16, and 6, in significant linkage with nodule mean volume (V), volume fraction, and number, respectively, and two loci on chromosomes 4 and 8 in suggestive linkage with V. These loci were differently positioned with respect to Hcs and Hcr loci mapped previously in backcross rats. On the basis of phenotypic and allele distribution patterns of BFF2 rats, loci on chromosomes 1 and 16 were identified as Hcs3 and Hcs4, and loci on chromosomes 4, 8, and 6 as Hcr4, Hcr5, and Hcr6. Additive interactions occurred between Hcs3 and Hcs4, and Hcr4 and a locus on chromosome 3 with less than suggestive linkage with V. All of the loci were in chromosomal regions syntenic to mouse and/or human chromosomal segments showing allelic gain or loss in hepatocellular carcinomas. These data indicate that inheritance of predisposition to rat liver tumor is characterized by the interplay of several genetic factors and suggest some possible mechanisms of polygenic control of human liver cancer.

Item Type:Article
ID Code:4323
Status:Published
Refereed:Yes
Uncontrolled Keywords:Carcinogens, chromosome mapping, diethylnitrosamine
Subjects:Area 06 - Scienze mediche > MED/04 Patologia generale
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
Publisher:American Association for Cancer Research
eISSN:0008-5472
Deposited On:20 Aug 2010 13:58

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