Role of Atp7b gene in spontaneous and N-diethylnitrosamine-induced carcinogenesis in a new congenic strain, WKAH.C-Atp7b rats.

Abstract

To examine whether Long-Evans Cinnamon (LEC) rats, a mutant rat model of Wilson's disease, have a susceptibility gene(s) to hepatocarcinogenesis in addition to the causative gene, Atp7b, we established a new congenic strain, WKAH.C-Atp7b rats, in which the Atp7b gene of the LEC rats is inserted into the normal Wistar-King Aptekman Hokkaido (WKAH) background. Hepatocellular tumors developed spontaneously in both sexes of WKAH.C-Atp7b rats, their incidence being slightly lower than that in LEC rats. Incidences of spontaneous liver tumors in LEC, WKAH.C-Atp7b and WKAH rats correlated with hepatic copper and iron concentrations. Medium-term liver bioassay showed that LEC rats were more susceptible to the induction of glutathione S-transferase placental form-positive preneoplastic foci than WKAH.C-Atp7b rats, and WKAH.C-Atp7b rats were more susceptible than WKAH rats. In an N-diethylnitrosamine (DEN)-induced long-term carcinogenicity study, 1) LEC rats were similarly or rather less susceptible to hepatocellular tumors than WKAH.C-Atp7b and WKAH rats, indicating that the progression of the preneoplastic foci to liver cancer in LEC rats was worse than that in WKAH.C-Atp7b and WKAH rats, 2) the incidences of kidney tumors in LEC and WKAH.C-Atp7b rats were higher than that in WKAH rats and high copper concentrations in the kidneys were observed in LEC and WKAH.C-Atp7b rats, 3) LEC rats were resistant to lung carcinogenesis. These data indicate that the susceptibility of LEC rats to liver and kidney carcinogenesis could be explained by Atp7b gene mutation and that the susceptibility to lung carcinogenesis is controlled by gene(s) other than Atp7b.

• Authors: T Minami, S Kaneda, T Otsuka, Z Jiao, Y Suzuki, T Yamada, K Matsumoto, K Izumi
• Journal: Japanese journal of cancer research : Gann (Jpn J Cancer Res) Vol. 92 Issue 8 Pg. 841-7 (Aug 2001) ISSN: 0910-5050 [Print] Japan
• PMID: 11509115 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Cation Transport Proteins
• Diethylnitrosamine
• Copper
• Adenosine Triphosphatases
• Copper-Transporting ATPases

Topics

• Adenosine Triphosphatases (physiology)
• Animals
• Body Weight
• Carcinogenicity Tests
• Carcinoma, Hepatocellular (chemically induced, genetics, pathology)
• Cation Transport Proteins (physiology)
• Copper (metabolism)
• Copper-Transporting ATPases
• Diethylnitrosamine (toxicity)
• Disease Susceptibility
• Female
• Kidney Neoplasms (chemically induced, genetics, metabolism, pathology)
• Liver Neoplasms (chemically induced, genetics, pathology)
• Male
• Phenotype
• Precancerous Conditions (genetics)
• Rats
• Rats, Inbred LEC
• Rats, Mutant Strains