Possible contribution of indomethacin to the carcinogenicity of nongenotoxic bladder carcinogens that cause bladder calculi.
Nongenotoxic bladder carcinogens that form bladder calculi have been concluded to be of low carcinogenic risk to humans because bladder stones would be expelled or surgically removed before they had a chance to exert their carcinogenic effect. It is the aim of this report to examine the possible contribution of indomethacin to the carcinogenic risk posed by nongenotoxic bladder carcinogens that cause bladder stones. Indomethacin may act as a tumor promoter in the bladder by interfering with the synthesis of prostaglandins. Prostaglandins have a cytoprotective function in the gastric mucosa and possibly also in the urinary bladder. Diminished cytoprotection may be implicated in bladder carcinogenesis as beta-naphthylamine, a human bladder carcinogen, also inhibits prostaglandin synthesis in vitro. The presence of other tumor promoters in the bladder may further ensure that tumors would be formed even if bladder stones were expelled. People who are exposed to nongenotoxic bladder carcinogens that are present in the environment and that form bladder stones, therefore, may be at an increased risk for developing bladder cancer if they are also exposed to tumor promoters, such as indomethacin.
Milman
Harry A
HA
ToxNetwork.com, Rockville, Maryland 20853, USA. hmilman@toxnetwork.com
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism; D003043:Cocarcinogenesis; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity*; D006801:Humans; D007213:Indomethacin / Q000633:toxicity*; D011453:Prostaglandins / Q000378:metabolism; D018570:Risk Assessment; D001744:Urinary Bladder Calculi / Q000139:chemically induced* / Q000150:complications / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000209:etiology* / Q000378:metabolism
D002273:Carcinogens; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D007213:Indomethacin