The very high level of liver cancer, and particularly of intra-and hepatic cholangiocellular carcinomas in many areas of South-East Asia is causally linked to endemic infection with trematode liver flukes. An animal model closely mirroring the disease in man has already been established utilizing the susceptibility of Syrian golden hamsters to Opisthorchis viverrini and chemical carcinogens. The primary aim of the proposed research is to experimentally determine the potential efficacy of removal of live parasite stimulus by antihelminthic chemotherapy as a control measure for the human situation. Male Syrian hamsters initiated with dihydroxy-di-n-propylnitrosamine and suffering parasite exposure for different periods will be administered the drug praziquantel and the resultant effect on neoplastic lesion development assessed. The influence of repeated infection and chemotherapy will also be investigated. Since the observed opisthorchiasis-dependent enhancement of neoplasia in both man and the hamster appears directly related to the hyperplastic and inflammatory effects of fluke infestation and may involve the pancreas and gallbladder in addition to hepatocellular and cholangiocellular compartments of the liver, attention will be concentrated on cell proliferation as assessed by bromodeoxyuridine incorporation and enzyme phenotype in all of the possible target tissues. A comparative morphologic/histochemical/immunohistochemical approach focusing on differences between normal, hyperplastic and preneoplastic/ neoplastic populations will be adopted. Assessment of the influence of modified glucose-6-phosphate dehydrogenase expression and therefore ribose unit phosphate production for DNA synthesis by treatment with the hormone dehydroepiandrosterone and inhibition of ornithine decarboxylase by 1.3-diaminopropane administration will also be included to cast further light on the role played by proliferation in the processes underlying enhancement of neoplasia in the hepatobiliary-pancreatic axis by Opisthorchis viverrini infestation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA050216-02
Application #
3194580
Study Section
Metabolic Pathology Study Section (MEP)
Project Start
1989-08-03
Project End
1991-07-31
Budget Start
1990-08-01
Budget End
1991-07-31
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Nagoya City University
Department
Type
DUNS #
City
Nagoya
State
Country
Japan
Zip Code