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Carcinogens and Chemical Causes

Donald F. McDonald, MD
JAMA. 1968;206(8):1774. doi:10.1001/jama.1968.03150080054012.
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The known and suspected causes of human bladder cancer fall into four groups: industrial chemicals, metabolites of foodstuffs, tobacco tar, and chronic mechanical stimulation.

It has been known since 189533 that chronic industrial exposure to certain dye intermediates is associated with a high incidence of transitional cell bladder tumors. Occupational bladder tumors occur after a mean exposure time of 22.9 years and may involve 26% of the workers.34 The commonest recognized cause of occupational bladder tumor is β-naphthylamine. A recently recognized cause of human bladder tumor is p-biphenylamine (xenylamine).35 Benzidine, α-naphthylamine, and auramine36 are also suspect. The common denominator of chemicals which cause human bladder cancer seems to be a structure embodying an aromatic amine which can be excreted as an orthohydroxylated urinary metabolite.37 Agents which cause human transitional cell tumors are unique, since they appear not to be carcinogenic to other tissues. Experiments in


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