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No correlation has been noted between cigarette smoking history and the quantity of benzo[a]pyrenemodified DNA found by either the ELISA (Perera, 1981) or the USERIA (Hsu et d , 1981) techniques in these tissues. Such data point out the large degree of tissue variability and especially genetic variability of drug metabolism within the human population. The human P-450 gene responsible for this metabolism has been cloned and characterized (Jaiswalet d,1985a). 4 Excretion Just as most chemical carcinogens are passively absorbed, so are they passively excreted, through the hepatobiliary system and feces, and also via urine, sweat, semen, menses, and milk.
Ribonucleoside or ribonucleotideformations 9. Glywside conjugations 10. "Water conjugations" E. Beyond Phase I1 metabolism 1. Coxygenations 2. Glucuronidations 3. Glycosidations 4. 4 PHARMACOKINETICS 1 41 are hown to metabolize: many drugs and laboratory reagents; small chemicals such as benzene, thiocyanate,or ethanol; polycyclic aromatic hydrocarbons such as benzo[a]pyrene, halogenated hydrocarbons such as polychlorinated and polybrominated biphenyls, herbicides, insecticides, and ingredients in soaps and deodorants; certain fungal toxins and antibiotics; many of the chemotherapeutic agents used to treat human cancer; strong mutagens such as nitrosamines; aminom dyes and diazo compounds; many chemicals found in cosmetics and per fumes;numerous aromatic amines, such as those found in hair dyes, nitro aromatics, and heterocyclics; N-acetylarylamines and nitrofurans; wood terpenes; epoxides, carbamates; alkyhalides; safrole derivatives; antioxidants, other food additives, and many ingredients of foodstuffs, fermented alcoholic beverages, and spices; both endogenous and synthetic steriods; prostaglanb, and other endogenous compounds such as biogenic amines, indoles, thyroxine, and fatty acids.
With regard to rates of metabolism of chemical d o g e n s , more than four orders of magnitude of yariation have been observed among non-human species, and variation of more than two orders of magnitude are to be expected within the human population. Although policies for limiting exposure to carcinogens are formulated on the basis of the average human, genetically determined individual differences in metabolism are large. These account for much of the variation in response to chemicals that is seen within the human population.
Comparative Carcinogenicity of Ionizing Radiation and Chemicals by National Council on Radiation Protection and Measurements