PMID- 34280354
OWN - NLM
STAT- MEDLINE
DCOM- 20210817
LR  - 20210817
IS  - 1872-7786 (Electronic)
IS  - 0009-2797 (Linking)
VI  - 346
DP  - 2021 Sep 1
TI  - Dichloromethane increases mutagenic DNA damage and transformation ability in 
      cholangiocytes and enhances metastatic potential in cholangiocarcinoma cell 
      lines.
PG  - 109580
LID - S0009-2797(21)00218-0 [pii]
LID - 10.1016/j.cbi.2021.109580 [doi]
AB  - Dichloromethane (DCM), a widely used chlorinated solvent, is classified by IARC 
      (2017) as probably carcinogenic to humans. Exposure to DCM has been associated 
      with increased incidence of cholangiocarcinoma (CCA) in humans. This study aimed 
      to investigate how DCM could contribute to CCA development by investigating the 
      effects of DCM on DNA damage and cell transformation in cholangiocytes (MMNK-1) 
      and on metastatic potential as measured by invasion and cell migration in 
      malignant CCA cell lines (HuCCA-1 and RMCCA-1). MMNK-1 cells treated with the 
      non-cytotoxic concentration of DCM (25 muM, 24 h) significantly increased the 
      levels of mutagenic DNA adducts including 8-hydroxydeoxyguanosine, 8-OHdG, 
      (1.84-fold, p < 0.01) and 8-nitroguanine (1.96-fold, p < 0.01) and enhanced cell 
      transformation by 1.47-fold (p < 0.01). In addition, the expression of various 
      genes involved in carcinogenesis, namely, NFE2L2 (antioxidative response), CXCL8 
      (inflammation), CDH1 (cell adhesion), MMP9 (tissue remodeling) and MKI67 (cell 
      proliferation) were altered in cholangiocytes treated with DCM. When MMNK-1 cells 
      were transformed by DCM, the expression of all the aforementioned genes was also 
      increased. In malignant cell lines (HuCCA-1 and RMCCA-1), DCM treatment resulted 
      in increased CXCL8 and MMP9 transcription and decreased CDH1 transcription 
      accompanied by increased invasion and migration capabilities of these cells. 
      Taken together, this study demonstrated that DCM exposure could be linked to the 
      development of CCA.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Buranarom, Angkhameen
AU  - Buranarom A
AD  - Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Laksi, 
      Bangkok, Thailand; Post-graduate Program in Environmental Toxicology, Chulabhorn 
      Graduate Institute, Laksi, Bangkok, Thailand; Center of Excellence on 
      Environmental Health and Toxicology (EHT), Thailand.
FAU - Navasumrit, Panida
AU  - Navasumrit P
AD  - Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Laksi, 
      Bangkok, Thailand; Post-graduate Program in Environmental Toxicology, Chulabhorn 
      Graduate Institute, Laksi, Bangkok, Thailand; Center of Excellence on 
      Environmental Health and Toxicology (EHT), Thailand.
FAU - Ngaotepprutaram, Thitirat
AU  - Ngaotepprutaram T
AD  - Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Laksi, 
      Bangkok, Thailand.
FAU - Ruchirawat, Mathuros
AU  - Ruchirawat M
AD  - Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Laksi, 
      Bangkok, Thailand; Center of Excellence on Environmental Health and Toxicology 
      (EHT), Thailand. Electronic address: mathuros@cri.or.th.
LA  - eng
PT  - Journal Article
DEP - 20210717
PL  - Ireland
TA  - Chem Biol Interact
JT  - Chemico-biological interactions
JID - 0227276
RN  - 0 (DNA Adducts)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (RNA, Messenger)
RN  - 588X2YUY0A (Methylene Chloride)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Transformation, Neoplastic/*drug effects
MH  - Cholangiocarcinoma/metabolism/pathology
MH  - DNA Adducts/analysis/metabolism
MH  - DNA Damage/*drug effects
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Interleukin-8/genetics/metabolism
MH  - Matrix Metalloproteinase 9/genetics/metabolism
MH  - Methylene Chloride/chemistry/*toxicity
MH  - NF-E2-Related Factor 2/genetics/metabolism
MH  - RNA, Messenger/metabolism
OTO - NOTNLM
OT  - 8-Nitroguanine
OT  - 8-OHdG
OT  - Cholangiocarcinoma
OT  - Dichloromethane
OT  - Risk factor
EDAT- 2021/07/20 06:00
MHDA- 2021/08/18 06:00
CRDT- 2021/07/19 20:10
PHST- 2021/03/05 00:00 [received]
PHST- 2021/06/22 00:00 [revised]
PHST- 2021/07/16 00:00 [accepted]
PHST- 2021/07/20 06:00 [pubmed]
PHST- 2021/08/18 06:00 [medline]
PHST- 2021/07/19 20:10 [entrez]
AID - S0009-2797(21)00218-0 [pii]
AID - 10.1016/j.cbi.2021.109580 [doi]
PST - ppublish
SO  - Chem Biol Interact. 2021 Sep 1;346:109580. doi: 10.1016/j.cbi.2021.109580. Epub 
      2021 Jul 17.