In Vitro Cytotoxicity and Adaptive Stress Responses to Selected Haloacetic Acid and Halobenzoquinone Water Disinfection Byproducts

Chemical Research in Toxicology
Erik ProcházkaFrederic D L Leusch

Abstract

The process of disinfecting drinking water inadvertently leads to the formation of numerous disinfection byproducts (DBPs). Some of these are mutagenic, genotoxic, teratogenic, and cytotoxic, as well as potentially carcinogenic both in vivo and in vitro. We investigated the in vitro biological activity of five DBPs: three monohaloacetic acids (monoHAAs) [chloroacetic acid (CAA), bromoacetic acid (BAA), and iodoacetic acid (IAA)] and two novel halobenzoquinones (HBQs) [2,6-dichloro-p-benzoquinone (DCBQ) and 2,6-dibromo-p-benzoquinone]. We focused particularly on cytotoxicity and induction of two adaptive stress response pathways: the oxidative stress responsive Nrf2/ARE and DNA-damage responsive p53 pathways. All five DBPs were cytotoxic to the Caco-2 cell line after a 4 h exposure, and all DBPs induced both of the adaptive stress response pathways, Nrf2/ARE and p53, in the micromolar range, as measured by two β-lactamase-based reporter gene assays. The decreasing order of potency for all three endpoints for the five DBPs was IAA ∼ BAA > DCBQ ∼ DBBQ > CAA. Induction of oxidative stress was previously proposed to be the molecular initiating event (MIE) for both classes of DBPs. However, comparing the levels of activation of the t...Continue Reading

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Citations

Sep 8, 2016·Organic Letters·Guilherme A M JardimEufrânio N da Silva Júnior
May 4, 2017·The Science of the Total Environment·ShihChi WengErnest R Blatchley
Dec 24, 2016·Environmental Science. Processes & Impacts·Peta A NealeFrederic D L Leusch
Nov 17, 2020·The Science of the Total Environment·Chang Gyun ParkYoung Jun Kim
Apr 25, 2021·Journal of Biomedical Materials Research. Part B, Applied Biomaterials·Gang ZhongMingfeng Chen
Jun 5, 2021·Biology of Reproduction·Andressa GonsioroskiJodi A Flaws
Nov 11, 2020·Environmental Science & Technology·David Ross HallHui Peng
Jul 3, 2018·Environmental Science & Technology·Shengkun DongMichael J Plewa

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