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

Abstract

Earlier reports revealed oxysterol metabolites of Opisthorchis spp. 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 to investigate, compare and contrast spectrograms of soluble extracts from Fasciola hepatica adult worms from bile ducts of cattle with those from O. viverrini and O.felineus from experimentally infected hamsters. F. hepatica and Opisthorchis spp. shared common compounds including oxysterol-like metabolites, bile acids and DNA-adducts, but the spectrometric profiles of F. hepatica included far fewer compounds than Opisthorchis species. These findings support the postulate that parasitic oxysterol-like metabolites could be related to carcinogenesis associated to infection and they point to a molecular basis for the differences among major groups of liver flukes concerning infection-induced malignancy.

Global changes in gene expression related to Opisthorchis felineus liver fluke infection reveal temporal heterogeneity of a mammalian host response

“…Additionally, evidence indicates that helminths produce metabolites that might interact with host DNA thereby triggering the carcinogenic process associated with opisthorchiasis. In particular, investigation of adult-worm lysates ( O. viverrini and OF) has identified novel oxysterol derivatives that are potential promutagenic compounds ( Gouveia et al, 2017 , Gouveia et al, 2020 ; Vale et al, 2013 ).…”

Cancerogenic parasites in veterinary medicine: a narrative literature review

“…Experimentally-induced cancer in rodent models shows that O. felineus carcinogenic properties are similar to those of O. viverrini and C. sinensis [62,[204][205][206][207]. However, no natural-occurring cases of biliary neoplasia in other non-human definitive hosts have been reported to date [13].…”

“…According to epidemiological research, this fluke infection is correlated to severe hepatobiliary illness, as well as being a risk factor for cholangiocarcinoma [ 9 , 200 , 203 ]. Experimentally-induced cancer in rodent models shows that O. felineus carcinogenic properties are similar to those of O. viverrini and C. sinensis [ 62 , 204 – 207 ]. However, no natural-occurring cases of biliary neoplasia in other non-human definitive hosts have been reported to date [ 13 ].…”

“…Although Fasciola spp. are closely related to the previously described liver trematodes, there is yet no conclusive evidence linking these parasites to human cancer [ 207 ]. Nonetheless, this fluke has occasionally been linked to human and animal disease complications, mostly as a cause of liver fibrosis and cirrhosis, comparable to what has been described in other closely related veterinary-relevant agents, such the giant liver fluke ( Fascioloides magna ) [ 210 , 211 , 214 , 215 ].…”