PMID- 23370535
OWN - NLM
STAT- MEDLINE
DCOM- 20130904
LR  - 20191210
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Linking)
VI  - 133
IP  - 7
DP  - 2013 Jul
TI  - Involvement of mtDNA damage elicited by oxidative stress in the arsenical skin 
      cancers.
PG  - 1890-900
LID - 10.1038/jid.2013.55 [doi]
AB  - Arsenic causes several human cancers. Arsenic-induced Bowen's disease (As-BD), 
      the most common arsenical cancer, is characterized by increased proliferation, 
      dysplasia, and individual cell apoptosis, all of which involve mitochondria. We 
      reported that arsenic causes aberrant keratinocyte proliferation through 
      mtTFA-mediated mitochondrial biogenesis in As-BD. Increasing mitochondrial 
      biogenesis causes cells to undergo oxidative stress. However, how arsenic induces 
      oxidative stress and causes mtDNA damage in arsenical cancers remains largely 
      unknown. Using tissues from As-BD patients and arsenic-treated keratinocytes, we 
      determined the oxidative stress, antioxidant enzymes, DNA-repair enzymes, and 
      8-hydroxy-2'-deoxyguanosine (8-OHdG) level in mtDNA by immunofluorescence, 
      real-time PCR, and western blot. The results showed that oxidative stress was 
      enhanced in both As-BD and arsenic-treated keratinocytes. Antioxidant enzymes 
      including manganese-superoxide anion and copper/zinc-superoxide anion and 
      DNA-repair enzymes were upregulated concomitantly in tissues and cells. In 
      arsenic-treated keratinocytes, increased mitochondrial oxidative stress and the 
      8-OHdG level in mtDNA were attenuated by pretreatment with ascorbic acid, a 
      potent antioxidant. Further, we found several somatic mutations in the ND4, ND5, 
      and ND6 genes of mtDNA in lesional but not in perilesional skin from As-BD 
      patients. Taken together, the results suggest that oxidative damage and mutations 
      to mtDNA might be involved in the arsenical skin cancers in the context of 
      mitochondrial biogenesis.
FAU - Lee, Chih-Hung
AU  - Lee CH
AD  - Department of Dermatology, Kaohsiung Municipal Hsiao-Kang Hospital and Kaohsiung 
      Medical University, Kaohsiung, Taiwan.
FAU - Wu, Shi-Bei
AU  - Wu SB
FAU - Hong, Chien-Hui
AU  - Hong CH
FAU - Chen, Gwo-Shin
AU  - Chen GS
FAU - Wei, Yau-Huei
AU  - Wei YH
FAU - Yu, Hsin-Su
AU  - Yu HS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130131
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (Antioxidants)
RN  - 0 (DNA, Mitochondrial)
RN  - 11062-77-4 (Superoxides)
RN  - 88847-89-6 (8-Hydroxy-2'-Deoxyguanosine)
RN  - EC 6.5.1.- (DNA Repair Enzymes)
RN  - G9481N71RO (Deoxyguanosine)
RN  - N712M78A8G (Arsenic)
SB  - IM
MH  - 8-Hydroxy-2'-Deoxyguanosine
MH  - Aged
MH  - Aged, 80 and over
MH  - Antioxidants/metabolism
MH  - Apoptosis/drug effects
MH  - Arsenic/*adverse effects/pharmacology
MH  - Bowen's Disease/*chemically induced/genetics/*physiopathology
MH  - Case-Control Studies
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - DNA Damage/*physiology
MH  - DNA Repair Enzymes/metabolism
MH  - DNA, Mitochondrial/genetics/*physiology
MH  - Deoxyguanosine/analogs & derivatives/metabolism
MH  - Humans
MH  - Keratinocytes/drug effects/metabolism/pathology
MH  - Middle Aged
MH  - Mutation/genetics
MH  - Oxidative Stress/*physiology
MH  - Skin Neoplasms/*chemically induced/genetics/*physiopathology
MH  - Superoxides/metabolism
EDAT- 2013/02/02 06:00
MHDA- 2013/09/05 06:00
CRDT- 2013/02/02 06:00
PHST- 2013/02/02 06:00 [entrez]
PHST- 2013/02/02 06:00 [pubmed]
PHST- 2013/09/05 06:00 [medline]
AID - S0022-202X(15)36323-5 [pii]
AID - 10.1038/jid.2013.55 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2013 Jul;133(7):1890-900. doi: 10.1038/jid.2013.55. Epub 2013 
      Jan 31.