RGD Reference Report - Genetic resistance to chemical carcinogen-induced preneoplastic hepatic lesions in DRH strain rats. - Rat Genome Database

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Genetic resistance to chemical carcinogen-induced preneoplastic hepatic lesions in DRH strain rats.

Authors: Zeng, ZZ  Higashi, S  Kitayama, W  Denda, A  Yan, Y  Matsuo, K  Konishi, Y  Hiai, H  Higashi, K 
Citation: Zeng ZZ, etal., Cancer Res 2000 Jun 1;60(11):2876-81.
RGD ID: 619609
Pubmed: (View Article at PubMed) PMID:10850431

DRH strain rats were established by inbreeding a closed colony of Donryu rats continuously fed the chemical hepatocarcinogen 3'-methyl-4-dimethylaminoazobenzene for over 10 years. They are highly resistant to chemical induction of liver cancer and preneoplastic lesions. We studied the genetic basis of DRH resistance to preneoplastic lesions by analyzing 108 (F344 x DRH)F2 male rats fed 3'-methyl-4-dimethylaminoazobenzene for 7 weeks. Five parameters of preneoplastic liver lesions were selected for quantitative analysis: (a) number of glutathione S-transferase placental form-positive foci per unit area of liver section; (b) percentage area occupied by the foci; (c) average size of foci; (d) glutathione S-transferase placental form mRNA level; and (e) gamma-glutamyltranspeptidase mRNA level. Furthermore, O6-methylguanine DNA methyltransferase and mannose 6-phosphatase/insulin-like growth factor 2 receptor mRNA levels were quantified. Composite interval mapping analysis showed that there were two remarkably significant clusters of quantitative trait loci affecting preneoplastic liver lesions on chromosomes 1 and 4. These clusters were designated collectively as Drh1 and Drh2, respectively. The functions of the recessive DRH allele of Drh1 and the semidominant DRH allele of Drh2 were to suppress the phenotypes of precancerous lesions. Each cluster showed two to three subpeaks in linkage likelihood plots, suggesting the presence of several closely linked quantitative trait loci affecting preneoplastic lesions. Possible candidate genes at each locus will be discussed. Expression of O6-methylguanine DNA methyltransferase and mannose 6-phosphatase/insulin-like growth factor 2 receptor did not affect DRH resistance to hepatocarcinogenesis, although they were polymorphic between DRH and F344 rats.



Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

QTLs
Hcar4  (Hepatocarcinoma resistance QTL 4)
Hcar5  (Hepatocarcinoma resistance QTL 5)
Hcar6  (Hepatocarcinoma resistance QTL 6)
Hcar7  (Hepatocarcinoma resistance QTL 7)
Hcar8  (Hepatocarcinoma resistance QTL 8)

Objects referenced in this article
Strain DRH.F344-(D1Mgh8-D1Mgh12)/Shigm null Rattus norvegicus
Strain DRH/Seac null Rattus norvegicus
Strain F344/NRrrc null Rattus norvegicus

Additional Information