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 CH₂Cl₂, CHCl₃ and BrCHCl₂ 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 BrCHCl₂. Low concentrations of BrCHCl₂ stimulated hyperproliferation of fibroblasts, the most probable consequence of which is regenerative proliferation related to collagen induction. Fibroblasts exposed to BrCHCl₂ 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.

Keywords::

• Collagen
• formaldehyde
• lung cancer
• p-nitrophenol hydrolase
• phosgene

Acknowledgments

Thanks to MSc. Victor Hernández Chávez for his valuable support to perform the staining and image capture of collagen.

Declaration of interest

This study was financed by Instituto Politécnico Nacional-Instituto de Ciencia y Tecnología del Gobierno del Distrito Federal, code 2008/30. M. Nájera-Martínez is a DSc student. PhD E. García-Latorre, DSc. E. Reyes-Maldonado, DSc M.L. Domínguez-López, and DSc A. Vega-López are fellows of Estímulos al Desempeño en Investigación and Comisión y Fomento de Actividades Académicas (Instituto Politécnico Nacional) and Sistema Nacional de Investigadores (SNI, CONACyT, México). The authors report no conflicts of interest.