Inactivation of antiadherence effect of bladder surface glycosaminoglycans as possible mechanism for carcinogenesis.
We have shown that the urinary bladder secretes and binds to its surface a glycosaminoglycan layer whose nonspecific antiadherence effect protects the bladder from infection and perhaps from stone formation. If bladder cancer is caused by agents present in the urine, as is widely believed, this mechanism may also protect against carcinogenesis. We performed the current study to determine whether suspected carcinogens or cocarcinogens in the urine gain access to the transitional cells by impairing or inactivating the surface antiadherence effect. Using an in vivo method to quantitate bacterial adherence to the rabbit bladder, we compared adherence in control and glycosaminoglycan-deficient bladders to adherence in bladders treated with one of several suspected urinary carcinogens. There were statistically significant differences between adherence in control bladders and adherence in bladders treated with the tryptophan metabolites 3-hydroxykynurenine and 3-hydroxyanthranilic acid, sodium cyclamate, and sodium saccharin. These data indicate that perhaps certain suspected urinary bladder carcinogens inactivate the anti-adherence effect of the glycosaminoglycan layer at the bladder surface and thereby penetrate to the transitional cells to exert their tumorigenic effects; or they may serve as cocarcinogens that inactivate the glycosaminoglycan barrier and permit other urinary carcinogens to transform the transitional cells.
D015095:3-Hydroxyanthranilic Acid / Q000494:pharmacology; D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects*; D003494:Cyclamates / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000502:physiology*; D007737:Kynurenine / Q000031:analogs & derivatives / Q000494:pharmacology; D009369:Neoplasms / Q000209:etiology*; D011817:Rabbits; D012439:Saccharin / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects* / Q000503:physiopathology
D003494:Cyclamates; D006025:Glycosaminoglycans; D015095:3-Hydroxyanthranilic Acid; C005045:3-hydroxykynurenine; D007737:Kynurenine; D012439:Saccharin