PMID- 37423394
OWN - NLM
STAT- MEDLINE
DCOM- 20230717
LR  - 20230718
IS  - 1872-7077 (Electronic)
IS  - 1382-6689 (Linking)
VI  - 101
DP  - 2023 Aug
TI  - Arsenic trioxide (ATO) up-regulates cytochrome P450 1A (CYP1A) enzymes in murine 
      hepatoma Hepa-1c1c7 cell line.
PG  - 104214
LID - S1382-6689(23)00156-4 [pii]
LID - 10.1016/j.etap.2023.104214 [doi]
AB  - Arsenic trioxide (ATO) is a highly toxic arsenical which has been successfully 
      exploited for treating acute promyelocytic leukemia (APL). Unfortunately, its 
      therapeutic efficacy is accompanied by serious toxicities with undeciphered 
      mechanisms. Cytochrome P450 1A (CYP1A) enzymes undergo modulation by arsenicals, 
      with ensuing critical consequences regarding drug clearance or procarcinogen 
      activation. Here, we investigated the potential of ATO to alter basal and 
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced CYP1A1/1A2 expressions. 
      Mouse-derived hepatoma Hepa-1c1c7 cells were exposed to 0.63, 1.25, and 2.5 muM 
      ATO with or without 1 nM TCDD. ATO increased TCDD-induced CYP1A1/1A2 mRNA, 
      protein, and activity. Constitutively, ATO induced Cyp1a1/1a2 transcripts and 
      CYP1A2 protein. ATO increased AHR nuclear accumulation and subsequently increased 
      XRE-luciferase reporter activity. ATO enhanced CYP1A1 mRNA and protein 
      stabilities. In conclusion, ATO up-regulates CYP1A in Hepa-1c1c7 cells 
      transcriptionally, post-transcriptionally, and post-translationally. Therefore, 
      ATO can be implicated in clearance-related interactions with CYP1A1/1A2 
      substrates, or in excessive activation of environmental procarcinogens.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - El-Ghiaty, Mahmoud A
AU  - El-Ghiaty MA
AD  - Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, 
      Alberta, Canada.
FAU - Alqahtani, Mohammed A
AU  - Alqahtani MA
AD  - Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, 
      Alberta, Canada.
FAU - El-Kadi, Ayman O S
AU  - El-Kadi AOS
AD  - Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, 
      Alberta, Canada. Electronic address: aelkadi@ualberta.ca.
LA  - eng
PT  - Journal Article
DEP - 20230707
PL  - Netherlands
TA  - Environ Toxicol Pharmacol
JT  - Environmental toxicology and pharmacology
JID - 9612020
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - S7V92P67HO (Arsenic Trioxide)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A2)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Aryl Hydrocarbon)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Cytochrome P-450 CYP1A1/genetics/metabolism
MH  - *Carcinoma, Hepatocellular/drug therapy/genetics
MH  - Arsenic Trioxide/pharmacology
MH  - Cytochrome P-450 Enzyme System/metabolism
MH  - Cytochrome P-450 CYP1A2/genetics
MH  - *Liver Neoplasms
MH  - Cell Line
MH  - *Polychlorinated Dibenzodioxins/toxicity
MH  - RNA, Messenger/genetics
MH  - Receptors, Aryl Hydrocarbon
OTO - NOTNLM
OT  - AHR
OT  - ATO
OT  - CYP1A1
OT  - CYP1A2
OT  - TCDD
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- 2023/07/10 00:41
MHDA- 2023/07/17 06:42
CRDT- 2023/07/09 19:25
PHST- 2023/04/10 00:00 [received]
PHST- 2023/07/03 00:00 [revised]
PHST- 2023/07/06 00:00 [accepted]
PHST- 2023/07/17 06:42 [medline]
PHST- 2023/07/10 00:41 [pubmed]
PHST- 2023/07/09 19:25 [entrez]
AID - S1382-6689(23)00156-4 [pii]
AID - 10.1016/j.etap.2023.104214 [doi]
PST - ppublish
SO  - Environ Toxicol Pharmacol. 2023 Aug;101:104214. doi: 10.1016/j.etap.2023.104214. 
      Epub 2023 Jul 7.