Carcinogens bladder

The past experience of the dyestuff industry in its use of dye intermediates such as ( -naphthyl amine and benzidine (4), known human bladder carcinogens (334—343), have led to studies as to whether or not handlers of dyes are exposed to medical ha2ards such as cancer, dermatitis, and other disorders (344-360). 

Imaoka S, Yoneda Y, Matsuda T et al. 1997. Mutagenic activation of minary bladder carcinogens by CYP4B1 and the presence of CYP4B1 in bladder mucosa. Biochemical Pharmacology 54(6) 677-683. 

Because of demonstrated potent carcinogenicity in multiple animal species, evidence of genotoxicity, and structural relationship to the known bladder carcinogen benzidine, DCB should be regarded as a probable human carcinogen and exposure by any route should be avoided. ... 

In another report three noninvasive papillary tumors of the bladder were identified in a screening of 540 MOCA workers two tumors occurred in men with completely normal urine screening who were under 30, had never smoked, and had no previous occupational exposure to known bladder carcinogens. ... 

Toxicology. p-Nitrobiphenyl (PNB) is a urinary bladder carcinogen in dogs. 

There are no reports on carcinogenicity of PNB in humans. However, PNB was used as an intermediate in the preparation of 4-amino-biphenyl, a recognized human bladder carcinogen, and bladder tumors found in men exposed to 4-aminobiphenyl may have been partially due to PNB. ... 

PBNA has been tested for carcinogenicity in a number of species without conclusive results. There was no evidence of carcinogenic activity in male or female rats or in male mice fed 2500 or 5000 ppm in the diet for 2 years. The lack of carcinogenicity in rats may be related to an inability to metabolize PBNA to the known animal and human urinary bladder carcinogen P-naphthylamine. There was equivocal evidence for carcinogenicity in female mice, as indicated by the occurrence of two rare kidney tumors. Chemical-related non-neoplastic lesions, including nephropathy, karyomegaly, and hyperplasia, occurred in the kidneys of both species. 

A number of epidemiological studies have observed a high excess of bladder tumors among o-toluidine-exposed workers, but in all studies there was concomitant exposure to various other potential bladder carcinogens." It has been noted, however, that the coexposures differed between smdies, and in cases with data on duration of exposure, the highest risk was observed in the subgroup with the longest duration of exposure. In one report, 13... 

Hicks, R.M., Wakefield, S.J., and Chowaniec, J. (1975). Evaluation of a new model to detect bladder carcinogens or co-carcinogens results obtained with saccheirine, cyclamate and cyclophosphamide, Chem.-Biol. Interactions 11,224. 

Zack and Gaffey (1983) reported the mortality status of 884 white men employed for at least one year between 1955 and 1977 by a chemical plant in Nitro, WV, USA, involved in the production of 2,4,5-trichlorophenol and 2,4,5-T. 4-Aminobiphenyl, a human bladder carcinogen (see lARC, 1982), was produced from 1941 to 1952 in this plant. There were nine cases of bladder cancer, with 0.91 expected deaths from cancer other than of the bladder were not in excess. One case of liposarcoma was reported among workers assigned to 2,4,5-T operations. Zack and Suskind (1980) reported cancer outcomes of a cohort of 121 males involved in a 1949 accident at the same plant. Followup revealed nine cancer deaths between 1949 and 1978, with 9.0 expected. Three of these were lymphatic or haematopoietic in origin (0.9 expected p = 0.047]), and one was a primary dermal fibrous histiocytoma (0.15 expected). 

A number of arylamines are potent bladder carcinogens such as 4-aminobiphenyl, 1-naphthylamine, and benzidine. Metabolic activation of these carcinogens requires the action of UDP-glucuronosyl transferase on N-hydroxyarylamines to form N-glucuronides. 

K2. Kerr, W. K., Barkin, M., Todd, 1. A. D., and Menczyk, Z., A hypernephroma associated with elevated levels of bladder carcinogens in the urine case report. Brit. ]. Urol. 35, 236-266 (1963). 

Secondary prevention occurs when a disease is detected early when the individual is asymptomatic. Medical screening is the periodic examination of an individual in order to detect preclinical disease. Examples of medical screening include use of urinary cytology in workers exposed to bladder carcinogens and mammography for asymptomatic cancer of the breast. 

The mechanism of chronic toxicity is related, but not identical. 2NA and other aromatic amines including benzidine and 4-aminobiphenyl are potent human urinary bladder carcinogens. Apparently the AT-hydroxy-2-naphthylamine is N-glucuronide and the product is transported from the liver to the urinary bladder, where the glucuronide can be hydrolyzed liberating N-hydroxy aromatic amine. This material is... 

Similar considerations apply to all aryl amine bladder carcinogens employed in the dye, rubber and leather industries51. Between 1930 and 1960, the toxic natures of many other coal-tar (aromatic) amino compounds, particularly azo dyes, were revealed52. 

I joined the Miller laboratory in September, 1952, and my first project was to synthesize 1-hydroxy-2-aminonaphthalene, a suspected carcinogenic metabolite of /3-naphthylamine (a bladder carcinogen). After many attempts to synthesize... 

Though the toxicity of xenobiotics is generally decreased by metabolism, some xenobiotic metabolites are more toxic than their parent compounds. As noted earlier, the metabolite of benzo (a) pyrene is a lung carcinogen. Similarly, it is the metabolite of 1-naphthylamine and not the parent compound that is a bladder carcinogen. 

---