title: Halomethane-induced cytotoxicity and cell proliferation in human lung MRC-5 fibroblasts and NL20-TA epithelial cells.
abstract: Halomethanes (HMs) can be formed during the chlorination process to obtain drinking water. In liver cells, HMs had been shown to be mutagenic and carcinogenic; however, their bioactivation by CYP 2E1 and GSTT1 is required. Although inhalation is the most common pathway of exposure, reports on the toxic effects induced by HMs in human lung are contradictory. The aim of this study was therefore to evaluate in vitro cytotoxicity and cell proliferation induced by CH(2)Cl(2), CHCl(3) and BrCHCl(2) in human lung NL20-TA epithelial cells and MRC-5 fibroblasts, and their relationship with CYP 2E1 and GSTT1 activity. High concentrations of these HMs induced cytotoxicity, particularly in cells treated with BrCHCl(2). Low concentrations of BrCHCl(2) stimulated hyperproliferation of fibroblasts, the most probable consequence of which is regenerative proliferation related to collagen induction. Fibroblasts exposed to BrCHCl(2) exhibited low levels of CYP 2E1 activity suggesting that released bromine is able to alter this activity by affecting the active site or auto regulating the activity itself. GSTT1 was up to ten times more active than CYP 2E1 in both cell lines, indicating that potential lung damage is due to formation of pro-carcinogens such as formaldehyde.
authors.affiliation: Laboratorio de Toxicología Ambiental, Departamento de Ingeniería en Sistemas Ambientales, México D.F., México.
authors.forename: Minerva
authors.initials: M
authors.lastname: Nájera-Martínez
authors.forename: Ethel A
authors.initials: EA
authors.lastname: García-Latorre
authors.forename: Elba
authors.initials: E
authors.lastname: Reyes-Maldonado
authors.forename: M Lilia
authors.initials: ML
authors.lastname: Domínguez-López
authors.forename: Armando
authors.initials: A
authors.lastname: Vega-López
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology*; D008697:Methane / Q000031:analogs & derivatives* / Q000633:toxicity*; D020545:Respiratory Mucosa / Q000166:cytology; D012235:Rhodamines / Q000494:pharmacology
chemical_list: D012235:Rhodamines; C022027:lissamine rhodamine B; D019392:Cytochrome P-450 CYP2E1; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase; D008697:Methane