Dimethylarsinic acid in drinking water changed the morphology of urinary bladder but not the expression of DNA repair genes of bladder transitional epithelium in F344 rats.
Inorganic arsenic increases urinary bladder transitional cell carcinoma in humans. In F344 rats, dimethylarsinic acid (DMA[V]) increases transitional cell carcinoma. Arsenic-induced inhibition of DNA repair has been reported in cultured cell lines and in lymphocytes of arsenic-exposed humans, but it has not been studied in urinary bladder. Should inhibition of DNA damage repair in transitional epithelium occur, it may contribute to carcinogenesis or cocarcinogenesis. We investigated morphology and expression of DNA repair genes in F344 rat transitional cells following up to 100 ppm DMA(V) in drinking water for four weeks. Mitochondria were very sensitive to DMA(V), and swollen mitochondria appeared to be the main source of vacuoles in the transitional epithelium. Real-time reverse transcriptase polymerase chain reaction (Real-Time RT PCR) showed the mRNA levels of tested DNA repair genes, ataxia telangectasia mutant (ATM), X-ray repair cross-complementing group 1 (XRCC1), excision repair cross-complementing group 3/xeroderma pigmentosum B (ERCC3/XPB), and DNA polymerase beta (Polbeta), were not altered by DMA(V). These data suggested that either DMA(V) does not affect DNA repair in the bladder or DMA(V) affects DNA repair without affecting baseline mRNA levels of repair genes. The possibility remains that DMA(V) may lower damage-induced increases in repair gene expression or cause post-translational modification of repair enzymes.
Wang
Amy
A
Department of Biomedical Sciences and Pathobiology, Virginia Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA. amywang@vt.edu
Wolf
Douglas C
DC
Sen
Banalata
B
Knapp
Geremy W
GW
Holladay
Steven D
SD
Huckle
William R
WR
Caceci
Thomas
T
Robertson
John L
JL
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D002101:Cacodylic Acid / Q000008:administration & dosage / Q000633:toxicity*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D016014:Linear Models; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D001743:Urinary Bladder / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019459:Urothelium / Q000378:metabolism* / Q000648:ultrastructure; D014617:Vacuoles / Q000187:drug effects / Q000648:ultrastructure; D014867:Water; D000076105:X-ray Repair Cross Complementing Protein 1
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C000619372:Xrcc1 protein, rat; D014867:Water; C072022:XPBC-ERCC-3 protein; D002101:Cacodylic Acid; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D004265:DNA Helicases