Pyruvate remediation of cell stress and genotoxicity induced by haloacetic acid drinking water disinfection by‐products

Environmental and Molecular Mutagenesis - Tập 54 Số 8 - Trang 629-637 - 2013
Azra Dad1,2, Clara H. Jeong2, Justin A. Pals2, Elizabeth D. Wagner2,3, Michael J. Plewa2,3
1COMSATS Institute of Information Technology, Islamabad, Pakistan
2Department of Crop Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois
3Safe Global Water Institute and NSF Science and Technology, Center of Advanced Materials for the Purification of Water with Systems, University of Illinois at Urbana-Champaign, Urbana, Illinois

Tóm tắt

Monohaloacetic acids (monoHAAs) are a major class of drinking water disinfection by‐products (DBPs) and are cytotoxic, genotoxic, mutagenic, and teratogenic. We propose a model of toxic action based on monoHAA‐mediated inhibition of glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) as a target cytosolic enzyme. This model predicts that GAPDH inhibition by the monoHAAs will lead to a severe reduction of cellular ATP levels and repress the generation of pyruvate. A loss of pyruvate will lead to mitochondrial stress and genomic DNA damage. We found a concentration‐dependent reduction of ATP in Chinese hamster ovary cells after monoHAA treatment. ATP reduction per pmol monoHAA followed the pattern of iodoacetic acid (IAA) > bromoacetic acid (BAA) >> chloroacetic acid (CAA), which is the pattern of potency observed with many toxicological endpoints. Exogenous supplementation with pyruvate enhanced ATP levels and attenuated monoHAA‐induced genomic DNA damage as measured with single cell gel electrophoresis. These data were highly correlated with the SN2 alkylating potentials of the monoHAAs and with the induction of toxicity. The results from this study strongly support the hypothesis that GAPDH inhibition and the possible subsequent generation of reactive oxygen species is linked with the cytotoxicity, genotoxicity, teratogenicity, and neurotoxicity of these DBPs. Environ. Mol. Mutagen. 54:629–637, 2013. © 2013 Wiley Periodicals, Inc.

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Tài liệu tham khảo

10.1021/es1000193

10.3233/JAD-2010-1375

10.1021/es051602r

10.1111/j.1742-4658.2005.05103.x

10.1136/oem.2010.062703

10.1093/aje/kwr419

10.1016/j.bbabio.2009.06.004

10.1353/dem.2005.0002

10.1002/jnr.21634

10.1016/j.watres.2007.01.032

10.1002/(SICI)1096-9926(199606)54:2<57::AID-TERA1>3.0.CO;2-1

10.1107/S0907444905042289

10.1021/es3024226

10.1002/1097-4547(20000815)61:4<409::AID-JNR7>3.0.CO;2-M

10.1007/s10552-008-9116-y

10.1002/tcm.10010

King WD, 2000, Case‐control study of colon and rectal cancers and chlorination by‐products in treated water, Cancer Epidemiol Biomarkers Prev, 9, 813

10.1186/1476-069X-10-S1-S3

Komaki Y, 2009, Comparative DNA Damage and Repair Kinetics Study in Mammalian Cells by Chloro‐, Bromo,‐ and Iodoacetic Acid. Environmental Mutagen Society 40th Annual Meeting

10.1021/es060353j

10.1016/j.bbrc.2007.10.199

Loudon GM., 1995, Organic Chemistry

10.1046/j.1471-4159.1997.69010285.x

McGuire MJ, 2002, Information Collection Rule Data Analysis

10.1002/em.20530

10.1074/jbc.M704199200

10.1016/j.reprotox.2010.08.002

10.1021/es2008159

10.1111/j.1749-6632.2010.05634.x

10.1016/B978-0-12-427150-0.50101-7

Plewa MJ, 2009, Mammalian Cell Cytotoxicity and Genotoxicity of Disinfection By‐Products, 134

10.1021/es049971v

10.1021/bk-2008-0995.ch003

10.1002/em.20585

10.1093/ije/dyp371

10.1002/(SICI)1096-9926(199606)53:6<352::AID-TERA6>3.0.CO;2-1

10.1016/B978-0-444-52272-6.00276-2

10.1016/j.mrrev.2007.09.001

10.1016/j.envres.2012.04.014

10.1002/em.10175

10.1021/tx0497705

10.1093/toxsci/kfq287

Smith HS., 1979, In vitro properties of epithelial cell lines established from human carcinomas and nonmalignant tissue, J Natl Cancer Inst, 62, 225

10.1002/(SICI)1098-2280(2000)35:3<206::AID-EM8>3.0.CO;2-J

10.1016/j.cellsig.2010.08.003

U.S. Environmental Protection Agency, 1998, Quantification of Cancer Risk from Exposure of Chlorinated Drinking Water

U.S. Environmental Protection Agency, 2006, National primary drinking water regulations: Stage 2 disinfectants and disinfection byproducts rule, Fed Reg, 71, 387

10.1097/01.ede.0000121380.02594.fc

10.1093/aje/kwj364

10.1039/9781847559746-00079

10.1002/(SICI)1098-2280(1998)32:4<360::AID-EM10>3.0.CO;2-T

10.1021/es304786b

10.1016/j.mrgentox.2010.08.014

10.1021/bk-2000-0761.ch019

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Thông tin xuất bản

Environmental and Molecular Mutagenesis

Tập 54 Số 8

629-637

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