Milman Harry A
ToxNetwork.com, Rockville, Maryland 20853, USA.
Drug Chem Toxicol. 2007;30(3):161-6. doi: 10.1080/01480540701374722.
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.
已形成膀胱结石的非基因毒性膀胱致癌物对人类致癌风险较低，因为膀胱结石在有机会发挥致癌作用之前就会被排出或通过手术切除。本报告的目的是研究吲哚美辛对导致膀胱结石的非基因毒性膀胱致癌物所构成致癌风险的可能影响。吲哚美辛可能通过干扰前列腺素的合成而在膀胱中充当肿瘤促进剂。前列腺素在胃黏膜中具有细胞保护功能，在膀胱中可能也有此功能。细胞保护作用减弱可能与膀胱癌发生有关，因为人类膀胱致癌物β-萘胺在体外也能抑制前列腺素合成。膀胱中其他肿瘤促进剂的存在可能进一步确保即使膀胱结石被排出也会形成肿瘤。因此，接触环境中存在的、会形成膀胱结石的非基因毒性膀胱致癌物的人群，如果同时接触肿瘤促进剂，如吲哚美辛，患膀胱癌的风险可能会增加。
