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EVALUATION OF THE CYTOTOXICITY OF DRINKING WATER DISINFECTION BYPRODUCTS (DBPS): TRIHALOMETHANES (THMS), HALONITROMETHANES (HNMS), AND HALOACETIC ACIDS (HAAS) IN NORMAL HUMAN COLON CELLS
Citation:
JONES, C., A. KHAMDY, K. SAWYER, S. VONG, M. MOYER, AND A. B. DEANGELO. EVALUATION OF THE CYTOTOXICITY OF DRINKING WATER DISINFECTION BYPRODUCTS (DBPS): TRIHALOMETHANES (THMS), HALONITROMETHANES (HNMS), AND HALOACETIC ACIDS (HAAS) IN NORMAL HUMAN COLON CELLS. Presented at Society of Toxicology Annual Meeting 2007, Charlotte, NC, March 25 - 29, 2007.
Impact/Purpose:
The study demonstrated a cytotoxic response of NCM460 cells to DBPs similar to that of non-human mammalian cells
Description:
Epidemiological studies have linked the consumption of chlorinated surface waters to an increased risk of colorectal cancer. THMs and HAAs were found to increase cancer in laboratory animals, but no toxicity studies exist for the recently identified HNMs. Normal Human colonocytes (NCM-460) were plated at 7000 cells/well and incubated for 24 hours at 37oC/5% CO2 after which the cells were exposed to THMs, HNMs, or HAAs at concentrations of 1.00E-07M -- 3.0E-03M for 72-96 hours. Cell density was quantified using a crystal violet staining procedure. The concentration of a chemical that induced a 50% inhibition of cell growth (IC50) when compared to the untreated cells was calculated. The HNM IC50 ranged between 1.30E-05 - 1.0E-4 M. Only tribromomethane and dibromochloromethane of the THM series exhibited cytotoxicity (~3.0E-03M). Enzymatic analysis demonstrated that NCM460 cells possessed GSTT-1 and CYP2E1 activity similar to that measured in the large intestine and suggests a capability to activate THMs to cytotoxic intermediates. Prior treatment of the HNMs and THMs with human microsome preparations did not alter their cytotoxicity. The IC50 for the HAAs ranged between 1.48E-05M -¿ 3.41 E-03M. In general, the order of cytotoxicity was HNMs>HAAs>THMs. Within a series, the cytotoxicity increased with the degree of bromination and decreased with increasing molecular weight. The study demonstrated a cytotoxic response of NCM460 cells to DBPs similar to that of non-human mammalian cells (Plewa, MJ et al., Environ. Sci. Technol. 2004, 38, 62-68) and suggests that they might prove useful in determining a mechanistic potential for the carcinogenicity of unregulated DBPs