Effects of co-administration of dietary sodium arsenate and 2,3-dimercaptopropane-1-sulfonic acid (DMPS) on the rat bladder epithelium.
Inorganic arsenic is a known human carcinogen, inducing tumors of the skin, urinary bladder and lung. It is metabolized to organic methylated arsenicals. 2,3-Dimercaptopropane-1-sulfonic acid (DMPS), a chelating agent, is capable of reducing pentavalent arsenicals to the trivalent state and binding to the trivalent species, and it has been used in the treatment of heavy metal poisoning in humans. Therefore, we investigated the ability of DMPS to inhibit the cytotoxicity and regenerative urothelial cell proliferation induced by arsenate administration in vivo. Female rats were treated for 4 weeks with 100 ppm As(V). DMPS (2800 ppm) co-administered in the diet significantly reduced the As(V)-induced cytotoxicity of superficial cells detected by scanning electron microscopy (SEM), and the incidence of simple hyperplasia observed by light microscopy and the bromodeoxyuridine (BrdU) labeling index. It also reduced the total concentration of arsenicals in the urine and the methylation of arsenic. There were no differences in oxidative stress as assessed by immunohistochemical staining for 8-hydroxy-2'-deoxyguanosine (8OHdG) of the bladder urothelium. No differences were detected in urine sediments between groups. These data suggest that DMPS has the ability to inhibit both arsenate-induced acute toxicity and regenerative proliferation of the rat bladder epithelium, most likely by decreasing exposure of the urothelium to trivalent arsenicals excreted in the urine. These data provide additional evidence that the effects of arsenate exposure in vivo do not appear to be related to oxidative effects on dG in DNA.
Department of Pathology and Microbiology and the Eppley Institute for Cancer Research, University of Nebraska Medical Center, Omaha, NE 68198-3135, United States.
Shugo
S
Suzuki
Lora L
LL
Arnold
Karen L
KL
Pennington
Satoko
S
Kakiuchi-Kiyota
Baowei
B
Chen
Xiufen
X
Lu
X Chris
XC
Le
Samuel M
SM
Cohen
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001149:Arsenates / Q000633:toxicity* / Q000652:urine; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D008855:Microscopy, Electron, Scanning; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D014494:Unithiol / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019459:Urothelium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D001149:Arsenates; D002614:Chelating Agents; D014494:Unithiol; C009277:sodium arsenate; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine