Bladder tumor

In 1969, a chronic toxicity study on a cyclamate saccharin (10 1) blend indicated bladder cancer problems in rats. Cyclamate was soon banned by the FDA, but saccharin remained an approved sweetener. In 1977, the FDA proposed a ban on saccharin because of the discovery of bladder tumors in some male rats fed with high doses of saccharin. Because no other nonnutritive sweetener was available at that time, the proposed ban faced strong opposition. 

Chronic animal studies of organophosphates are few in number, but those that do exist provide a useful base from which to draw toxicological insight. In rats and mice exposed orally to tricresyl phosphate for 2 years, endocrine effects were found in a dose-response pattern and hepatic effects were found. Ovarian interstitial hyperplasia was also observed but was not dose related. No chronic-duration MRLs could be derived because of the limited number of studies. Tricresyl phosphate, a component of certain hydraulic fluids, produced no evidence of carcinogenic activity in assays with rats and mice (NTP 1994). However, another component, tributyl phosphate, was associated with an increased incidence of bladder tumors in rats and mice (FMC 1994a, 1994b). 

It is recommended that daily saccharin intake be maintained below 1 g because of a risk of bladder cancer. A lifetime daily diet containing 5-7.5% saccharin has induced bladder tumors in rats [69]. However, it is probable that saccharin is only a very weak carcinogen in humans. The amount contained in pharmaceutical preparations is well below the recommended maximum human daily intake. 

Bladder tumor-associated antigen (BTA), a human complement factor H, is produced by bladder cancer cells (men two to three times as often as women). Cancer cells are sometimes seen in urine samples by microscope cytoscopy (examination of the bladder with an instrument inserted into the urethra), which can reveal abnormal areas. Biopsy is needed to confirm the diagnosis. Early stage cancer confined to the bladder wall can often be removed with a cytoscope. If several tumors are present, they are removed by infusing the bladder with a solution containing bacteria able to stimulate the immune system. 

The most common BTA test is an immunoassay-based assay that uses monoclonal antibodies to detect the presence of bladder tumor-associated antigen in urine. In clinical studies, the BTA test was compared with cytoscopy-voided urine for the detection of recurrent bladder cancer. The sensitivity of BTA appeared su-... 

Comparison between Bladder Tumor-Associated Antigen (BTA) and Cytology... 

Sarosdy, M. F., deVere, R. W Soloway, M. S. Sensitivity of bladder tumor-associated antigen compared to cytology. J. Urol. 154, 379-384 (1995). 

The answer is i. (Katzwng, p 984.) Bacille Calmette-Guerin vaccine is a nonspecific stimulant of the reticuloendothelial system. It is an attenuated strain of Mycobacterium fruvis that appears most effective in small, localized bladder tumors. This agent is approved for intravesicular use in bladder cancer. Adverse reactions are associated with the renal system, such as problems with urination, infection, and cystitis. 

Historically, bladder tumors have been associated with exposures in the aniline dye industry. However, conclusive evidence for any one particular exposure could not be obtained in these studies since the workers were exposed to many chemicals within the same work area. For example, Case et al. (1954) investigated the incidence of bladder tumors among British workers in the chemical dye industry. In addition to aniline, the workers were exposed to other aromatic amines, including a- and P-naphthylamine, benzidine, and auramine. Although exposures could not be quantified, there was insufficient evidence to suggest that aniline was a cause of bladder cancers. More recent studies indicate that P-naphthylamine, 4-aminodiphenyl, 4-nitrodiphenyl, 4,4-diaminodiphenyl, or o-toluidine may be involved in increased cancers in the dye industry (Ward et al. 1991 Benya and Cornish 1994). 

Antibiotic prophylaxis is warranted in high-risk patients (e.g., prolonged indwelling catheterization, positive urine cultures, and neutropenia) undergoing transurethral, perineal, or suprapubic resection of the prostate, resection of bladder tumors, or cystoscopy. 

Haaff, E.O., Caralona, W.J., and Ratliff, T.L., Detection of interleukin-2 in the urine of patients with superficial bladder tumors after treatment with intravesical BCG, J. Urol., 136, 970, 1986. 

Oncogenic mutations P21 (ros) Colon, lung, breast, bladder tumors... 

Table 6.2 Dose-response relationship for saccharin-induced bladder tumors in rats...

Expressed as concentration of saccharin in diets of test animals (per cent of diet). Number of animals diagnosed with bladder tumors after a lifetime of exposure, with exposures beginning in utero. 

Kurlyandskiy BA, Medvedovskiy AG, Genin VA, et al. 1976. Experimental study of the combined effect of some diphenyl amino derivatives for the purpose of preventing occupational bladder tumors. Gig tr Prof Zabol 5 34-38. (Russian)... 

Shabad LM, Genin VA. 1975. Combined action of amino-substituted biphenyl causing bladder tumors. Urol Nefrol 1 38-42. (Russian)... 

In one of these reports, no bladder tumors were foimd in a group of 35 workers who handled only 3,3 -dichlorobenzidine in the same dyestuff plant, bladder tumors occurred in 3 out of 14 workers exposed to both benzidine and 3,3 -dichlorobenzidine. The investigator reported a total exposure time of 68,505 hours, equivalent to nearly 140 full-time working years (Gadian 1975). 

No cases of bladder tumors were found in an epidemiology study of 259 workers exposed to dry and semi-dry 3,3 -dichlorobenzidine base and hydrochloride. Cytological analyses of the urine (Papanicolaou tests) were negative. Workers were exposed to an average of less than 16 years each to 3,3 -dichloro-benzidine, which means that an adequate exposure dmation and/or the latent period following exposm-e may not have been reached for tumor expression (MacIntyre 1975). 

Stula EF, Barnes JR, Sherman H, et al. 1978. Liver and urinary bladder tumors in dogs from 3,3 -dichlorobenzidine. J Environ Pathol Toxicol l(4) 475-490. 

Intratracheal administration of 5-15 mg AAF one to two times per week for 17 months in hamsters (total dose 1100 mg) caused bladder tumors in 10 of 23 animals all mmors were transitional cell carcinomas with or without focal squamous cell carcinomas. ... 

Of 171 workers exposed to 4-amin-odiphenyl for 1.5-19 years, 11% had bladder tumors the tumors appeared 5-19 years after initial exposure. ... 

Melick WF et al The first reported cases of human bladder tumors due to a new carcinogen - xenylamine. 7 Urol 74 760-766, 1955... 

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