Association of liver fluke (Opisthorchis viverrini) infestation with increased expression of cytochrome p450 and carcinogen metabolism in male hamster liver1,2

Kirby, Gordon M., Pelkonen, Paivi, Vatanasapt, Vanchai, Camus, Anne-Marie, Wild, Christopher P. and Lang, Matti A. (1994) Association of liver fluke (Opisthorchis viverrini) infestation with increased expression of cytochrome p450 and carcinogen metabolism in male hamster liver1,2. Molecular Carcinogenesis, 11 2: 81-89.


Author Kirby, Gordon M.
Pelkonen, Paivi
Vatanasapt, Vanchai
Camus, Anne-Marie
Wild, Christopher P.
Lang, Matti A.
Title Association of liver fluke (Opisthorchis viverrini) infestation with increased expression of cytochrome p450 and carcinogen metabolism in male hamster liver1,2
Formatted title Association of liver fluke (Opisthorchis viverrini) infestation with increased expression of cytochrome p450 and carcinogen metabolism in male hamster liver1,2
Journal name Molecular Carcinogenesis   Check publisher's open access policy
ISSN 0899-1987
1098-2744
Publication date 1994-10
Sub-type Article (original research)
DOI 10.1002/mc.2940110205
Volume 11
Issue 2
Start page 81
End page 89
Total pages 9
Place of publication Hoboken, NJ, United States
Publisher John Wiley and Sons
Language eng
Abstract Synergy between exposure to chemical carcinogens (nitrosamines) and infestation with the liver fluke Opisthorchis viverrini has been demonstrated in a hamster model of hepatocarcinogenesis (Flavell et al., Carcinogenesis 4:927–930, 1983; Thamavit et al., Carcinogenesis 8:1351–1353, 1987). to elucidate the mechanisms of this interaction we tested the hypothesis that liver parasitism might influence the expression and activity of carcinogen metabolizing enzymes. We found that one, and perhaps more, hamster liver cytochrome P450 (CYP) isozymes immunorelated to mouse CYP2A5 contributed up to 50 or 60% of the hepatic aflatoxin B1(AFB) and N-nitrosodiethylamine (NDEA) metabolism, respectively. As inferred from average enzyme activities and from western blot, immunoinhibition, and substrate (coumarin) inhibition analyses, O. viverrini infestation increased the expression of enzymes detectable by anti-CYP2A5 antibody as well as NDEA metabolism in male but not in female hamsters. Immunohistochemical analysis of CYP2A expression by anti-mouse CYP2A5 antibody demonstrated that the O. viverrini-associated increase was not uniformly distributed throughout the lever but occurred in hepatocytes immediately adjacent to areas of inflammation. Immunohistochemical analysis of AFB-DNA adducts in the livers of O. viverrini-infested hamsters treated with AFB showed that the highest levels of adducts were found in the regions of liver where hepatocellular expression of enzymes detectable by anti-CYP2A5 antibody is induced. These results suggest that a high local expression of CYP isozymes in O. viverrini-infested livers could be a contributing risk factor in the development of liver cancers associated with paraitic hepatitis.
Keyword Immunohistochemistry
Aflatoxin B1-DNA adducts
Cytochrome P540
Local expression
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: National Research Centre for Environmental Toxicology Publications
 
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