Bladder cancer aromatic amines

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). 

Increased risk of hydralazine-induced lupus, increased levels of isoniazid with an increased risk of neurotoxicity, increased risk of bladder cancer in individuals exposed to aromatic amines Increased risk of serious toxicity to mercaptopurine and azathioprine... 

Saffiotti U, Cells F, Montesano R, et al. 1967. Induction of bladder cancer in hamsters fed aromatic amines. In Deichman WB, Lampke KF, eds. Bladder cancer A symposium. Birmingham, AL Aesculapius Publishing Co. 129-135. 

Stern FB, Murthy LI, Beaumont JJ, et al Notification and risk assessment for bladder cancer of a cohort exposed to aromatic amines. III. Mortality among workers exposed to aromatic amines in the last 3-naphthylamine manufacturing facility in the United States. Occup Med27-.495-500, 1985... 

Ward, E.M., Sabbioni, G, DeBoiti, D.G, Teass, A.W., Brown, K.K., Talaska, GG, Roberts, D.R., Ruder, A M. Streicher, R.P. (1996) Monitoring of aromatic amine exposure in workers at a chemical plant with a known bladder cancer excess. J. natl Cancer Inst., 88, 1046-1052... 

Some other aromatic amines such as benzidine and 4-aminobiphenyl are also carcinogenic to the bladder by the same mechanism. These amines have industrial uses and have been implicated in bladder cancer in exposed humans. 

Aromatic amines Bladder cancer Slow acetylators... 

With aromatic amines such as benzidine, 4-aminobiphenyl and 2-aminonaphthalene, which cause bladder cancer, epidemiological evidence suggests that those with the slow acetylator phenotype who have occupational exposure are more at risk. In contrast, with the heterocyclic amines produced in food by cooking, such as PhIP, which cause colon cancer, it seems from similar evidence that fast acetylators are more at risk. 

DOT CLASSIFICATION 6.1 Label KEEP AWAY FROM FOOD SAFETY PROFILE Confirmed carcinogen with experimental tumorigenic data. Along with p-naphthylamine and benzidine, it has been incriminated as a cause of urinary bladder cancer. Poison by subcutaneous and intraperitoneal routes. Moderately toxic by ingestion. Mutation data reported. Combustible when exposed to heat or flame. Incompatible with nitrous acid. To fight fire, use dry chemical, CO2, mist, spray. When heated to decomposition it emits toxic fumes of NOx. See also 2-NAPHTHYLAMINE and AROMATIC AMINES. 

A3a. Allen, M. J., Boyland, E., Dukes, C. E., Homing, E. S., and Watson, J. G., Cancer of the urinary bladder induced in mice with metabolites of aromatic amines and tryptophan. Brit. ]. Cancer 11, 212-228 (1957). 

The discovery that exposure to exogenous chemicals could lead to cancer in humans was first made in the late 18th century, when Percival Pott demonstrated the relationship between cancer of the scrotum and the occupation of chimney sweepers exposed to coal tar/soot. Other examples noted later were scrotal cancers in cotton spinners exposed to unrefined mineral oils, and cancers of the urinary bladder in men who worked in textile dye and rubber industries due to their exposure to certain aromatic amines used as antioxidants. Experimental induction of cancer by chemicals was first reported in detail by Yamagiwa and Ichikawa in 1918, when repeated application of coal tar to the ear of rabbits resulted in skin carcinomas. Over the next few years, Kennaway and Leitch confirmed this finding and demonstrated similar effects in mice and rabbits from the application of soot extracts, other types of tar (e.g., acetylene or isoprene), and some heated mineral oils. These researchers also observed skin irritation sometimes accompanied by ulcers at the site of application of the test material. Irritation was thought to be an important factor in skin tumor development. However, not all irritants (e.g., acridine) induced skin cancer in mice and conversely, some purified chemicals isolated from these crude materials... 

One common polymorphism in the United States is for N-acetyltransferase, an enzyme involved in phase II reactions. N-acetyltransferase catalyzes the acetylation of aromatic amines and hydrazines, and other classes of xenobiotics. People characterized as slow acetylators have relatively low N-acetytransf-erase activity. Consequently, slow acetylators are more sensitive to the toxic effects of certain types of drugs, including sulfa drugs. In addition, a study of workers exposed to benzidine in the dye industry suggested a link between the slow acetylator phenotype and the development of bladder cancer. 

Carcinogenic properties are dependent on individual rates of acetylation. Persons who are slow acetylators are more susceptible to bladder cancer from aromatic amines, as generally are workers in industrialized countries. Nutrition is also implicated in the development of cancer by polycyclic aromatic amines. 

PHS is suspected of contributing to bladder cancer in dogs by converting aromatic amines to reactive radicals through one-electron oxidation in the liver. 

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