title: Bromodichloromethane induces cell proliferation in different tissues of male F344 rats by suppression of E-cadherin expression via hypermethylation or transcriptional activation of c-myc and cyclin D1.
abstract: The aim of this study was to investigate the mechanism of bromodichloromethane (BDCM) - induced cell proliferation in different tissues of male F344 rats. Rats were administered at doses of 0 and 100mg/kg/day BDCM dissolved in corn oil by gavage for 5 days/week for 1, 4, 8 and 12 weeks. Then the colon, kidney and liver were collected. No histologic lesions were observed in the colon of rats exposed to BDCM, while there were mild nephrotoxicity and marginal hepatotoxicity related to BDCM treatment. Moreover, BDCM enhanced cell proliferation in the colon and kidney but not in the liver. In colons, hypermethylation in E-cadherin promoter might be associated with inhibition of mRNA and protein expression after 12 weeks of BDCM exposure. In kidneys, BDCM decreased E-cadherin mRNA expression, accompanying with transcriptional activation of c-myc and cyclin D1. However, suppression of E-cadherin mRNA and protein expression occurred in the absence of significant changes in DNA methylation. Therefore, suppression of E-cadherin expression via hypermethylation or transcriptional activation of c-myc and cyclin D1 may be involved in BDCM-induced cell proliferation in different tissues of male F344 rats.
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, PR China; The Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liao
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.forename: Shun-Chang
authors.initials: SC
authors.lastname: Zhou
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.forename: Ai-Lin
authors.initials: AL
authors.lastname: Liu
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Lu
mesh_terms: D000818:Animals; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects*; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003314:Corn Oil; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D015533:Transcriptional Activation; D022882:Trihalomethanes / Q000633:toxicity
chemical_list: D015820:Cadherins; D002273:Carcinogens; C530106:Ccnd1 protein, rat; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D022882:Trihalomethanes; D019938:Cyclin D1; C025191:bromodichloromethane; D003314:Corn Oil
keywords: Adenomatous polyposis coli; Bromodichloromethane; Cadherins; Cell proliferation; DNA methylation; Rats