Development of normal human colon cell cultures to identify priority unregulated disinfection byproducts with a carcinogenic potential

ENVR 106

Anthony DeAngelo, deangelo.anthony@epa.gov1, Carlton Jones1, Sheau-Fung Thai1, Yue Ge1, and Mary Moyer2. (1) National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, 108 TWAlexander Drive, Research Triangle Park, NC 27711, (2) INCELL Corporation, San Antonio, TX 78249
NCM460 colonocytes, a normal stem cell line, are being used to identify DBPs with the ability to transform human colonocytes into malignant cells. NCM460 cells exhibit a life cycle similar to that in situ and possess GSTT-1 and CYP2E1 activity similar to that measured in the large intestine so possess the capability to activate or detoxify xenobiotics. The halonitromethanes (HNMs) were selected for study and are being compared to trihalomethanes (THMs) and haloacetic acids (HAAs), some of whose members were demonstrated to induce colon cancer in laboratory animals. NCM460 cells were exposed to 1E-06 M azoxymethane (AOM), bromochloroacetic acid (BCA), dibromonitromethane and tribromonitromethane for 10 days. AOM and BCA were found to induce colon cancer in rats. Cells growing in suspension from all chemical treatments were sub-cultured and tested for the ability to form colonies when grown in soft agar, a characteristic of transformation. All test compouns were positive (untreated cells did not form colonies). Microarray analyses performed on NCM460 cells following treatment with the test chemicals showed an up regulation of the Wnt signaling pathway and cell-cell adherens gene expression for all treatments.
 

Advances in Drinking Water Disinfection and Disinfection Byproduct Management
8:30 AM-12:10 PM, Tuesday, April 8, 2008 Morial Convention Center -- Rm. 236, Oral

Division of Environmental Chemistry

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008