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Association of liver fluke ( Opisthorchis viverrini ) infestation with increased expression of cytochrome p450 and carcinogen metabolism in male hamster liver 1,2
Author(s) -
Kirby Gordon M.,
Pelkonen Päivi,
Vatanasapt Vanchai,
Camus AnneMarie,
Wild Christopher P.,
Lang Matti A.
Publication year - 1994
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940110205
Subject(s) - opisthorchis viverrini , biology , hamster , cytochrome p450 , carcinogen , opisthorchis , mesocricetus , isozyme , microbiology and biotechnology , liver fluke , enzyme , biochemistry , immunology , helminths
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 B 1 (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. ©1994 Wiley‐Liss, Inc.