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bioRxiv · 10.1101/606772

Helminth infection-induced carcinogenesis: spectrometric insights from the liver flukes, Opisthorchis and Fasciola

Gouveia, M. J.·Pakharukova, M. Y.·Sripa, B.·Rinaldi, G.·Brindley, P. J.·Mordvinov, V. A.·Gärtner, F.·Costa, J. M. C. d.·Vale, N.
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Abstract

Chronic infections with the flatworm parasites Opisthorchis viverrini, Clonorchis sinensis and Schistosoma haematobium are classified as group 1 biological carcinogens, i.e. definitive causes of cancer. In addition, we reported findings that support the inclusion of Opisthorchis felineus in this list of biological carcinogens. By contrast, infections with close phylogenetic relatives including Fasciola hepatica have not been associated with carcinogenesis. Earlier reports revealed of oxysterol metabolites of Opisthorchis liver fluke origin conjugated with DNA bases, suggesting that the generation of these DNA-adducts may underlie the mutagenicity and carcinogenicity of the infection with these food-borne pathogens. Here we employed liquid chromatography-mass spectrometry (LC-MS/MS) to investigate, compare and contrast spectrograms of soluble extracts from F. hepatica adult worms from bile ducts of cattle with those from O. viverrini and O. felineus from experimentally-infected hamsters. F. hepatica displayed a complex spectrophotometric profile. F. hepatica and Opisthorchis spp. shared several common compounds including oxysterol-like metabolites, bile acids and DNA-adducts, but the spectrometric profiles of these Opisthorchis species included far fewer compounds than F. hepatica. These findings support the postulate that oxysterol-like metabolites of parasite origin can initiate carcinogenesis and they point to a molecular basis for the inconsistencies among major groups of liver flukes concerning infection-induced malignancy.\n\nAuthor SummarySeveral species of trematodes are parasites of the human hepatobiliary tract. Infection with two of these flukes, Clonorchis sinsensis and Opisthorchis viverrini, fresh water fish-borne parasites that occur in East Asia is classified as group 1 carcinogens by the International Agency for Research on Cancer (IARC), i.e. definitive causes of cancer in humans. By contrast, infection with a different liver fluke, Fasciola hepatica, does not lead to malignant transformation of the biliary tract. Given the close phylogeny of all three parasites, this difference in carcinogenicity is intriguing and, if explained, likely of value in novel therapeutic approaches. The importance of the current findings is informative because they present a mass spectrometric analysis and catalog of the similarities and differences between fluke of the genus Opisthorchis and F. hepatica, potentially identifying carcinogenic metabolites of liver fluke origin. These metabolites can be expected to provide deeper understanding of helminth infection induced malignancy.

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Gouveia, M. J., Pakharukova, M. Y., Sripa, B., Rinaldi, G., Brindley, P. J., Mordvinov, V. A., Gärtner, F., Costa, J. M. C. d., Vale, N.. 2019-04-11. Helminth infection-induced carcinogenesis: spectrometric insights from the liver flukes, Opisthorchis and Fasciola. https://doi.org/10.1101/606772

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