Metabolic activation of N-nitrosamine drinking water disinfection byproducts and their induction of genomic DNA damage in mammalian cells

ENVR 108

Kang-Mei Hsu, khsu3@uiuc.edu1, William A. Mitch, gh17@umail.umd.edu2, Elizabeth D. Wagner, edwagner@uiuc.edu1, and Michael J. Plewa, mplewa@uiuc.edu1. (1) Department of Crop Sciences, & Center of Advanced Materials for the Purification of Water with Systems, University of Illinois at Urbana-Champaign, 1101 West Peabody Dr, Urbana, IL 61801, (2) Department of Chemical Engineering, Yale University, 9 Hillhouse Avenue, Mason Lab 313b, New Haven, CT 06520
N-nitrosodimethylamine (NDMA) is a drinking water DBP and is listed by the EPA as a probable human carcinogen. NDMA is found in chloraminated drinking water, where the nitrogen in monochloramine (NH2Cl) is incorporated into the structure of the by-product. Currently five nitrosamine DBPs have been found in finished drinking water (NDMA, N-nitrosopyrrolidine, N-nitrosomorpholine, N-nitrosopiperidine and N-nitrosodiphenylamine). Unlike the majority of DBPs, nitrosamines require metabolic activation to be converted into their ultimate toxic forms. We are developing and calibrating a monooxygenase-dependent (S9) activation protocol for Chinese hamster ovary (CHO) cells to study the induction of genomic DNA by nitrosamine DBPs. Genomic damage is measured using the single-cell gel electrophoresis assay (SCGE or Comet assay). Currently our S9 modifications have increased the sensitivity of the in vitro SCGE assay in mammalian cells by >300x for NDMA as compared to published data.
 

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