PMID- 36516492
OWN - NLM
STAT- MEDLINE
DCOM- 20230105
LR  - 20230111
IS  - 1879-2448 (Electronic)
IS  - 0043-1354 (Linking)
VI  - 229
DP  - 2023 Feb 1
TI  - Comparative cytotoxicity, endocrine-disrupting effects, oxidative stress of 
      halophenolic disinfection byproducts and the underlying molecular mechanisms 
      revealed by transcriptome analysis.
PG  - 119458
LID - S0043-1354(22)01403-8 [pii]
LID - 10.1016/j.watres.2022.119458 [doi]
AB  - Halophenolic disinfection byproducts (DBPs) are a class of emerging pollutants 
      whose adverse effects on human cells and the underlying molecular mechanisms 
      still need further exploration. In this study, we found that when halophenolic 
      DBPs were substituted with the same halogen, the more substitution sites, the 
      more cytotoxic, while when they were substituted at the same sites, the most 
      toxic chemical was iodophenols, followed by bromophenols and chlorophenols. In 
      addition, several of them exerted significant endocrine-disrupting effects at 
      sublethal concentrations. 2,4,6-triiodophenol (TIP) and 2,4-dichlorophenol 
      (2,4-DCP) showed the highest estradiol equivalent factor (EEF) of 4.41 x 10(-8) 
      and flutamide equivalent factor (FEF) of 0.4, respectively. Furthermore, all of 
      the halophenolic DBPs except for 2-chlorophenol (2-CP) and 2-bromophenol (2-BP) 
      significantly increased the levels of reactive oxygen species (ROS) or 
      8-hydroxydeoxyguanosine (8-OHdG) in HepG2 cells. The lowest cytotoxicity and 
      unchanged ROS and 8-OHdG levels after 2-CP exposure may result from the 
      activation of the transporters of the adenosine triphosphate (ATP) binding 
      cassette in cells. Transcriptome analysis revealed distinct grouping patterns of 
      2-CP, 2,6-dibromophenol (2,6-DBP), and TIP at the concentrations of EC(20), and 
      the top differentially expressed genes (DEGs) were involved in the antioxidant-, 
      immune-, and endocrine-associated systems. The weighted gene correlation network 
      analysis well connected the phenotypes (EC(50), EEF, FEF, ROS, 8-OHdG, and ABC 
      transporters) with the DEGs and revealed that the MAPK signaling pathway played a 
      vital role in regulating the biological response after exposure to halophenolic 
      DBPs. This study provides deep insights into the underlying mechanisms of the 
      toxic effects induced by halophenolic DBPs.
CI  - Copyright (c) 2022 Elsevier Ltd. All rights reserved.
FAU - Li, Xiuwen
AU  - Li X
AD  - State Key Laboratory of Pollution Control and Resource Reuse, School of the 
      Environment, Nanjing University, 163 Xianlin Road, Nanjing 210023, China.
FAU - Gao, Xinran
AU  - Gao X
AD  - State Key Laboratory of Pollution Control and Resource Reuse, School of the 
      Environment, Nanjing University, 163 Xianlin Road, Nanjing 210023, China.
FAU - Li, Aimin
AU  - Li A
AD  - State Key Laboratory of Pollution Control and Resource Reuse, School of the 
      Environment, Nanjing University, 163 Xianlin Road, Nanjing 210023, China.
FAU - Xu, Shuhui
AU  - Xu S
AD  - State Key Laboratory of Pollution Control and Resource Reuse, School of the 
      Environment, Nanjing University, 163 Xianlin Road, Nanjing 210023, China.
FAU - Zhou, Qing
AU  - Zhou Q
AD  - State Key Laboratory of Pollution Control and Resource Reuse, School of the 
      Environment, Nanjing University, 163 Xianlin Road, Nanjing 210023, China. 
      Electronic address: zhouqin@nju.edu.cn.
FAU - Zhang, Lulu
AU  - Zhang L
AD  - State Key Laboratory of Pollution Control and Resource Reuse, School of the 
      Environment, Nanjing University, 163 Xianlin Road, Nanjing 210023, China.
FAU - Pan, Yang
AU  - Pan Y
AD  - State Key Laboratory of Pollution Control and Resource Reuse, School of the 
      Environment, Nanjing University, 163 Xianlin Road, Nanjing 210023, China.
FAU - Shi, Wei
AU  - Shi W
AD  - State Key Laboratory of Pollution Control and Resource Reuse, School of the 
      Environment, Nanjing University, 163 Xianlin Road, Nanjing 210023, China.
FAU - Song, Maoyong
AU  - Song M
AD  - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research 
      Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 
      100085, China.
FAU - Shi, Peng
AU  - Shi P
AD  - State Key Laboratory of Pollution Control and Resource Reuse, School of the 
      Environment, Nanjing University, 163 Xianlin Road, Nanjing 210023, China. 
      Electronic address: shipeng@nju.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20221204
PL  - England
TA  - Water Res
JT  - Water research
JID - 0105072
RN  - 0 (Disinfectants)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Water Pollutants, Chemical)
SB  - IM
MH  - Humans
MH  - Disinfection
MH  - *Disinfectants/toxicity/chemistry
MH  - Reactive Oxygen Species
MH  - Halogenation
MH  - *Water Pollutants, Chemical/chemistry
MH  - Oxidative Stress
MH  - Gene Expression Profiling
MH  - *Water Purification
OTO - NOTNLM
OT  - Cytotoxicity
OT  - Endocrine-disrupting effects
OT  - Halophenolic disinfection byproducts
OT  - Transcriptomics
OT  - WGCNA
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/12/15 06:00
MHDA- 2023/01/06 06:00
CRDT- 2022/12/14 18:03
PHST- 2022/08/23 00:00 [received]
PHST- 2022/10/30 00:00 [revised]
PHST- 2022/12/03 00:00 [accepted]
PHST- 2022/12/15 06:00 [pubmed]
PHST- 2023/01/06 06:00 [medline]
PHST- 2022/12/14 18:03 [entrez]
AID - S0043-1354(22)01403-8 [pii]
AID - 10.1016/j.watres.2022.119458 [doi]
PST - ppublish
SO  - Water Res. 2023 Feb 1;229:119458. doi: 10.1016/j.watres.2022.119458. Epub 2022 
      Dec 4.