Human Carcinogens

Alkylating chemotherapy agents: Cyclophospha-mide, melphalan.

Aromatics: Aromatic amines, benzene, benzidene, polycyclic aromatic hydrocarbons (PAHs).

Environmental toxins: Aflatoxins, tobacco smoke, tars, soots, hydrocarbon, dry cleaning and degreasing solvents = carbon tetrachloride (CCl4), perchloroethylene, trichloroethylene, trichloroethane.

Hormones: Estrogens (diethyl stilbesterol), anabolic steroids. Plastics: Vinyl chloride monomer, aryl acrylates. Heavy metals: Arsenic, chromium, nickel. Ionizing radiation: Radon, x-rays. Nonionizing radiation: Ultraviolet light. Miscellaneous drugs: Chloramphenicol, phenytoin. Industrial exposures: Arsenic, asbestos, cadmium, chromium, nickel, silica.

Antimetabolites: Example = methotrexate (MTX), a dihydrofolate reductase (DHFR) and thymidine synthetase inhibitor that prevents activated, reduced folate from serving as a cofactor for DNA and RNA synthesis. Overdose causes diffuse mucositis, myelosuppres-sion, acute renal failure, and death, usually from sepsis.

Antimitotics: Examples = vincristine (VCR) and vinblastine (VB), both vinca plant alkaloids that inhibit microtubular polymerization and arrest mitosis at metaphase, limiting cell movement and cell division. Overdoses cause seizures, encephalopathy, autonomic dysfunction, myelosuppression, and inappropriate secretion of antidiuretic hormone.

Antibiotics: Two main classes = (1) the true anthracyclines = daunorubicin, doxorubicin, and (2) the mycins = adriamycin, bleomycin, mithramycin, mitomycin. Most antineoplastic antibiotics are derived from the Streptomyces bacterium and release oxygen (O-) free radicals (similar to paraquat), causing severe cardiotox-icity, parenchymal pulmonary toxicity, mucosi-tis, and myelosuppression. Alkylating agents: Two main classes = (1) nitrogen mustards, like cyclophosphamide and chlor-ambucil, can cause hemorrhagic cystitis and myelosuppression on overdose; and (2) heavy metal platinoids, like cisplatin and carboplatin, can cause seizures, encephalopathy, retinal tox-icity, ototoxicity, and peripheral neuropathy on overdose.

TABLE 11.1 Classification of Anti-Cancer Agents and Their Toxicities

Class

Agent

Toxicity

Overdose

Antidote

Chlorambucil

Cyclophosphamide

Hemorrhagic cystitis, encephalopathy, pulmonary fibrosis

Seizures, myocardial necrosis

Benzodiazepines

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