PRINCIPLES OF TOXICOLOGY - Biology East Borneo

13.10 CANCER TRENDS AND THEIR IMPACT ON EVALUATION OF CANCER CAUSATION 319TABLE 13.19 Pharmaceutical Agents a with Carcinogenic Effects bGeneric Name Therapeutic Use Daily Dosage (mg/day) Tumor Site; SpeciesRifampin Antibiotic: tuberculosis 600 Liver; miceIsoniazid Antibiotic: tuberculosis 300 Lung; miceClofibrate Lowers cholesterol 2000 Liver; miceDisulfiram Discourages alcohol abuse 125–500 Liver; ratsPhenobarbital Antiepileptic 100–200 Liver; miceAcetaminophen Pain relief (OTC) 2000–4000 Liver; miceMetronidazole Antibiotic, antiparasitic 500 Lung; rats/miceSulfisoxazole Antibiotic, urinary tract 8000Dapsone Antibacterial, AIDS, leprosy, etc. 300 Spleen, thyroid, andperitoneum; ratsMethimazole Hypothyroidism 15 Thyroid and pituitarytumors; ratsOxazepam Antianxiety 70 Thyroid, testes,prostate; rats/miceliver; miceFurosemide Water retention in disease states 75a List adapted from Waddell (1996).b Cancer effects as listed in the Physicians Desk Reference (PDR), 1996, or Ames and Gold (1991).tic agents used to treat cancer. Many antineoplastic drugs are potent genotoxic chemicals, and theirdamage to DNA in rapidly dividing cells like cancer cells is a primary feature of both their therapeuticeffects and toxicities. Admittedly, it may be well worth a theoretical risk of developing cancer 20 yearsafter taking medication to cure a current case of cancer, however, a number of drugs whose therapeuticbenefits are directed at less serious health conditions are also known to have carcinogenic effects inhumans or in animal cancer bioassays. Some potentially carcinogenic pharmaceuticals are listed inTable 13.19.Not only are many of the drugs listed in Table 13.19 commonly prescribed, but the single dailydoses of these chemicals are large relative to the doses of chemicals one is typically concerned withwhen evaluating environmental pollutants. Thus, the theoretical risks associated with even limitedtherapy may approach or exceed the theoretical risks posed by the environmental contamination weare often concerned about when remediating sites that contain these contaminants.13.10 CANCER TRENDS AND THEIR IMPACT ON EVALUATION OF CANCERCAUSATIONHuman Cancer Trends in the United StatesAs mentioned regarding smoking, the incidence of cancer in this nation has remained stable, ordeclined, for most types of cancer according to the American Cancer Society. The greatest exceptionis, of course, lung cancer in both males and females. A 1998 report from the National Cancer Institute(NCI) (see Table 13.20) indicated that after increasing 1.2 percent per year from 1973 to 1990,incidence for all cancers combined declined in the United States an average of 0.7 percent from 1990to 1995. Cancer mortality similarly declined about 0.5 percent per annum for the same period(1990–1995). Cancers of the lung, breast, prostate, and colon–rectum accounted for over half of thenew cases. Cancer of the lung, both incidence and mortality, is actually showing a slight decline whilein women, such cancers (and the resultant mortality) are still on the increase. Incidence and mortality