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Infection with carcinogenic helminth parasites and its production of metabolites induces the formation of DNA-adducts

2019-11-29Journal article Open access
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dc.contributor.authorGouveia, Maria João
dc.contributor.authorBrindley, Paul J.
dc.contributor.authorRinaldi, Gabriel
dc.contributor.authorGärtner, Fátima
dc.contributor.authorda Costa, José M.C.
dc.contributor.authorVale, Nuno
dc.date.accessioned2020-05-10T09:06:02Z
dc.date.available2020-05-10T09:06:02Z
dc.date.issued2019-11-29
dc.description.abstractBackground: Infections classified as group 1 biological carcinogens include the helminthiases caused by Schistosoma haematobium and Opisthorchis viverrini. The molecular mediators underlying the infection with these parasites and cancer remain unclear. Although carcinogenesis is a multistep process, we have postulated that these parasites release metabolites including oxysterols and estrogen-like metabolites that interact with host cell DNA. How and why the parasite produce/excrete these metabolites remain unclear. A gene encoding a CYP enzyme was identified in schistosomes and opisthorchiids. Therefore, it is reasonable hypothesized that CYP 450 might play a role in generation of pro-inflammatory and potentially carcinogenic compounds produced by helminth parasites such as oxysterols and catechol estrogens. Here, we performed enzymatic assays using several isoforms of CYP 450 as CYP1A1, 2E1 and 3A4 which are involved in the metabolism of chemical carcinogens that have been associated with several cancer. The main aim was the analysis of the role of these enzymes in production of helminth-associated metabolites and DNA-adducts. Method: The effect of cytochrome P450 enzymes CYP 1A1, 2E1 and 3A4 during the interaction between DNA, glycocholic acid and taurochenodeoxycholate sodium on the formation of DNA-adducts and metabolites associated with urogenital schistosomiasis (UGS) and opisthorchiasis was investigated in vitro. Liquid chromatography/mass spectrometry was used to detect and identify metabolites. Main findings: Through the enzymatic assays we provide a deeper understanding of how metabolites derived from helminths are formed and the influence of CYP 450. The assays using compounds similar to those previously observed in helminths as glycocholic acid and taurochenodeoxycholate sodium, allowed the detection of metabolites in their oxidized form and their with DNA. Remarkably, these metabolites were previously associated with schistosomiaisis and opisthorchiasis. Thus, in the future, it may be possible to synthesize this type of metabolites through this methodology and use them in cell lines to clarify the carcinogenesis process associated with these diseases. Principal conclusions: Metabolites similar to those detected in helminths are able to interact with DNA in vitro leading to the formation of DNA adducts. These evidences supported the previous postulate that imply helminth-like metabolites as initiators of helminthiases-associated carcinogenesis. Nonetheless, studies including these kinds of metabolites and cell lines in order to evaluate its potential carcinogenic are required.pt_PT
dc.description.sponsorshipThis work was financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia, in the framework of the project, Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). The FCT and FEDER (European Union) also supported these studies through project number IF/00092/2014/CP1255/CT0004pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationInfect Agent Cancer. 2019 Nov 29;14:41. doi: 10.1186/s13027-019-0257-2. eCollection 2019pt_PT
dc.identifier.doi10.1186/s13027-019-0257-2pt_PT
dc.identifier.issn1750-9378
dc.identifier.urihttp://hdl.handle.net/10400.18/6644
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherBMCpt_PT
dc.relation.publisherversionhttps://infectagentscancer.biomedcentral.com/articles/10.1186/s13027-019-0257-2pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectHelminth Infectionpt_PT
dc.subjectCytochrome P450pt_PT
dc.subjectMalignancypt_PT
dc.subjectOpisthorchiasispt_PT
dc.subjectOxysterolpt_PT
dc.subjectSchistosomiasispt_PT
dc.subjectInfecções Sistémicas e Zoonosespt_PT
dc.titleInfection with carcinogenic helminth parasites and its production of metabolites induces the formation of DNA-adductspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue1pt_PT
oaire.citation.startPage41pt_PT
oaire.citation.titleInfectious Agents and Cancerpt_PT
oaire.citation.volume14pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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