title: Biological mechanism for the toxicity of haloacetic acid drinking water disinfection byproducts.
abstract: The halogenated acetic acids are a major class of drinking water disinfection byproducts (DBPs) with five haloacetic acids regulated by the U.S. EPA. These agents are cytotoxic, genotoxic, mutagenic, and teratogenic. The decreasing toxicity rank order of the monohalogenated acetic acids (monoHAAs) is iodo- > bromo- >> chloroacetic acid. We present data that the monoHAAs inhibit glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity in a concentration-dependent manner with the same rank order as above. The rate of inhibition of GAPDH and the toxic potency of the monoHAAs are highly correlated with their alkylating potential and the propensity of the halogen leaving group. This strong association between GAPDH inhibition and the monoHAA toxic potency supports a comprehensive mechanism for the adverse biological effects by this widely occurring class of regulated DBPs.
authors.affiliation: College of Agricultural, Consumer, and Environmental Sciences, Department of Crop Sciences, and the NSF WaterCAMPWS Center, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Pals
authors.forename: Justin K
authors.initials: JK
authors.lastname: Ang
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Wagner
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Plewa
mesh_terms: D000085:Acetates / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004202:Disinfectants / Q000378:metabolism / Q000633:toxicity*; D004586:Electrophoresis; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors*; D006019:Glycolysis / Q000187:drug effects*; D054879:Halogenation; D007700:Kinetics; D008954:Models, Biological; D015394:Molecular Structure; D018675:Toxicity Tests / Q000379:methods; D014881:Water Supply / Q000592:standards*
chemical_list: D000085:Acetates; D004202:Disinfectants; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases