PMID- 22178741
OWN - NLM
STAT- MEDLINE
DCOM- 20120416
LR  - 20131121
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 259
IP  - 1
DP  - 2012 Feb 15
TI  - Inorganic arsenic in drinking water accelerates 
      N-butyl-N-(4-hydroxybutyl)nitrosamine-induced bladder tissue damage in mice.
PG  - 27-37
LID - 10.1016/j.taap.2011.11.016 [doi]
AB  - Epidemiological studies have revealed that exposure to an arsenic-contaminated 
      environment correlates with the incidence of bladder cancer. Bladder cancer is 
      highly recurrent after intravesical therapy, and most of the deaths from this 
      disease are due to invasive metastasis. In our present study, the role of 
      inorganic arsenic in bladder carcinogenesis is characterized in a mouse model. 
      This work provides the first evidence that inorganic arsenic in drinking water 
      promotes N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced bladder tissue 
      damage, including the urothelium and submucosal layer. This damage to the bladder 
      epithelium induced by BBN includes thickening of the submucosal layer, the loss 
      of the glycosaminoglycan layer and an increase in both the deoxyguanosine 
      oxidation and cytosine methylation levels in the DNA. Further, when 10ppm 
      inorganic arsenic is combined with BBN, the number of bladder submucosal 
      capillaries is increased. In addition, inorganic arsenic also increases the 
      deoxyguanosine oxidation level, alters the cytosine methylation state, decreases 
      the activities of glutathione reductase and glucose-6-phosphate dehydrogenase, 
      decreases the protein expression of NAD(P)H quinone oxidoreductase-1 (NQO-1) and 
      increases the protein expression of specific protein 1 (Sp1) in bladder tissues. 
      In summary, our data reveal that inorganic arsenic in drinking water promotes the 
      BBN-induced pre-neoplastic damage of bladder tissue in mice, and that the 
      8-hydroxy-2'-deoxyguanosine, 5-methylcytosine, NQO-1 protein and Sp1 protein 
      levels may be pre-neoplastic markers of bladder tumors.
CI  - Copyright A(c) 2011 Elsevier Inc. All rights reserved.
FAU - Lin, Paul-Yann
AU  - Lin PY
AD  - Department of Pathology, Chang Gung Memorial Hospital at Chiayi, Chang Gung 
      University, Chiayi, Taiwan.
FAU - Lin, Yung-Lun
AU  - Lin YL
FAU - Huang, Chin-Chin
AU  - Huang CC
FAU - Chen, Sin-Syu
AU  - Chen SS
FAU - Liu, Yi-Wen
AU  - Liu YW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111208
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Antioxidants)
RN  - 0 (Arsenites)
RN  - 0 (Sp1 Transcription Factor)
RN  - 0 (Water Pollutants, Chemical)
RN  - 3817-11-6 (Butylhydroxybutylnitrosamine)
RN  - 8J337D1HZY (Cytosine)
RN  - G9481N71RO (Deoxyguanosine)
SB  - IM
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Arsenites/*toxicity
MH  - Blotting, Western
MH  - Body Weight/drug effects
MH  - Butylhydroxybutylnitrosamine/*toxicity
MH  - Cocarcinogenesis
MH  - Cytosine/metabolism
MH  - DNA Damage
MH  - DNA Methylation
MH  - Deoxyguanosine/metabolism
MH  - Drug Synergism
MH  - Female
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Sp1 Transcription Factor/metabolism
MH  - Urinary Bladder/*drug effects/enzymology/metabolism/pathology
MH  - Urinary Bladder Neoplasms
MH  - Water Pollutants, Chemical/*toxicity
EDAT- 2011/12/20 06:00
MHDA- 2012/04/17 06:00
CRDT- 2011/12/20 06:00
PHST- 2011/07/24 00:00 [received]
PHST- 2011/11/23 00:00 [revised]
PHST- 2011/11/25 00:00 [accepted]
PHST- 2011/12/20 06:00 [entrez]
PHST- 2011/12/20 06:00 [pubmed]
PHST- 2012/04/17 06:00 [medline]
AID - S0041-008X(11)00452-2 [pii]
AID - 10.1016/j.taap.2011.11.016 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2012 Feb 15;259(1):27-37. doi: 
      10.1016/j.taap.2011.11.016. Epub 2011 Dec 8.