Folic acid supplementation during early hepatocarcinogenesis: cellular and molecular effects

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorAndrade Chagas, Carlos Eduardo
dc.creatorBassoli, Bruna Kempfer
dc.creatorSoares de Souza, Camila Alexandre
dc.creatorDeminice, Rafael
dc.creatorJordao Junior, Alceu Afonso
dc.creatorPaiva, Sergio Alberto Rupp de
dc.creatorZaidan Dagli, Maria Lucia
dc.creatorOng, Thomas Prates
dc.creatorMoreno, Fernando Salvador
dc.date2014-05-20T13:33:18Z
dc.date2016-10-25T16:51:23Z
dc.date2014-05-20T13:33:18Z
dc.date2016-10-25T16:51:23Z
dc.date2011-11-01
dc.date.accessioned2017-04-05T20:23:27Z
dc.date.available2017-04-05T20:23:27Z
dc.identifierInternational Journal of Cancer. Malden: Wiley-blackwell, v. 129, n. 9, p. 2073-2082, 2011.
dc.identifier0020-7136
dc.identifierhttp://hdl.handle.net/11449/11386
dc.identifierhttp://acervodigital.unesp.br/handle/11449/11386
dc.identifier10.1002/ijc.25886
dc.identifierWOS:000295230500003
dc.identifierhttp://dx.doi.org/10.1002/ijc.25886
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/859157
dc.descriptionFolic acid (FA) supplementation during carcinogenesis is controversial. Considering the impact of liver cancer as a public health problem and mandatory FA fortification in several countries, the role of FA supplementation in hepatocarcinogenesis should be elucidated. We evaluated FA supplementation during early hepatocarcinogenesis. Rats received daily 0.08 mg (FA8 group) or 0.16 mg (FA16 group) of FA/100 g body weight or water (CO group, controls). After a 2-week treatment, animals were subjected to the "resistant hepatocyte" model of hepatocarcinogenesis (initiation with diethylnitrosamine, selection/promotion with 2-acetylaminofluorene and partial hepatectomy) and euthanized after 8 weeks of treatment. Compared to the CO group, the FA16 group presented: reduced (p < 0.05) number of persistent and increased (p < 0.05) number of remodeling glutathione S-transferase (GST-P) positive preneoplastic lesions (PNL); reduced (p < 0.05) cell proliferation in persistent GST-P positive PNL; decreased (p < 0.05) hepatic DNA damage; and a tendency (p < 0.10) for decreased c-myc expression in microdissected PNL. Regarding all these parameters, no differences (p > 0.05) were observed between CO and FA8 groups. FA-treated groups presented increased hepatic levels of S-adenosylmethionine but only FA16 group presented increased S-adenosylmethionine/S-adenosylhomocysteine ratio. No differences (p > 0.05) were observed between experimental groups regarding apoptosis in persistent and remodeling GST-P positive PNL, and global DNA methylation pattern in microdissected PNL. Altogether, the FA16 group, but not the FA8 group, presented chemopreventive activity. Reversion of PNL phenotype and inhibition of DNA damage and of c-myc expression represent relevant FA cellular and molecular effects.
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.languageeng
dc.publisherWiley-Blackwell
dc.relationInternational Journal of Cancer
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectfolic acid supplementation
dc.subjecthepatocarcinogenesis
dc.subjectchemoprevention
dc.subjectpreneoplastic lesions
dc.titleFolic acid supplementation during early hepatocarcinogenesis: cellular and molecular effects
dc.typeOtro


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