{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:16:26Z","timestamp":1792174586925,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,9,24]],"date-time":"2012-09-24T00:00:00Z","timestamp":1348444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["MOP-77596"],"award-info":[{"award-number":["MOP-77596"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:sec><jats:title>Scope<\/jats:title><jats:p>Inadequate folate intake increases risk for colorectal cancer. We previously showed that low\u2010folate diets induced intestinal tumors in <jats:styled-content style=\"fixed-case\">BALB<\/jats:styled-content>\/c mice, but not in <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6 mice. We suggested that <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> damage, altered methylation, and reduced apoptosis could contribute to tumorigenesis in this model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>To identify genes involved in tumorigenesis, we compared gene expression profiles in preneoplastic intestine of <jats:styled-content style=\"fixed-case\">BALB<\/jats:styled-content>\/c and C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6 mice\u2010fed low folate. We identified 74 upregulated and 90 downregulated genes in <jats:styled-content style=\"fixed-case\">BALB<\/jats:styled-content>\/c compared to <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6 mice. We validated decreased expression of <jats:italic><jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>cmo1<\/jats:italic> and increased expression of <jats:italic><jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>ldh1a<\/jats:italic>, which would be expected to upregulate the peroxisome proliferator\u2010activated receptor alpha (<jats:styled-content style=\"fixed-case\">PPARA<\/jats:styled-content>) pathway, and confirmed the expected upregulation of several <jats:italic><jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>para<\/jats:italic> downstream genes. We verified, in <jats:styled-content style=\"fixed-case\">BALB<\/jats:styled-content>\/c mice, reduced expression of <jats:italic><jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>prr2a<\/jats:italic>, a gene that increases resistance to oxidative damage, and of two oncosuppressors (<jats:italic><jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>mp5<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>rntl<\/jats:italic>). Low folate increased <jats:italic><jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>para<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>ldh1a1<\/jats:italic> expression, and decreased <jats:italic><jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>cmo1, <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>prr2a,<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>mp5<\/jats:italic> expression in <jats:styled-content style=\"fixed-case\">BALB<\/jats:styled-content>\/c, compared to <jats:styled-content style=\"fixed-case\">BALB<\/jats:styled-content>\/c on control diets. <jats:italic><jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>cmo1, <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>para<\/jats:italic>, and <jats:italic><jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>mp5<\/jats:italic> showed differential <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation related to strain, diet, and\/or <jats:italic><jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>thfr<\/jats:italic> genotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Disturbed regulation of the retinoid\/<jats:styled-content style=\"fixed-case\">PPARA<\/jats:styled-content> pathway, which influences oxidative damage, and altered expression of tumor suppressors may contribute to intestinal tumorigenesis induced by low\u2010folate intake.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.201200212","type":"journal-article","created":{"date-parts":[[2012,9,24]],"date-time":"2012-09-24T08:53:31Z","timestamp":1348476811000},"page":"686-697","source":"Crossref","is-referenced-by-count":19,"title":["Differential gene expression and methylation in the retinoid\/<scp>PPARA<\/scp> pathway and of tumor suppressors may modify intestinal tumorigenesis induced by 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