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Part III. Chemistry, host entry, and metabolic fate of carcinogens
Author(s) -
Falk Hans L.,
Kotin Paul
Publication year - 1963
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt19634188
Subject(s) - carcinogen , respiratory tract , cigarette smoke , gastrointestinal tract , chemistry , endogeny , metabolism , carcinogenesis , respiratory system , pharmacology , physiology , cancer research , biology , toxicology , biochemistry , anatomy , gene
The skin, respiratory tract, and gastrointestinal tract are the organ systems through which environmental carcinogenic agents gain entry into the host. Of the several sources of carcinogenic agents, this report is concerned with the two most common in the respiratory environment—urban polluted air and cigarette smoke. Carcinogenic polycyclic aromatic hydrocarbons (PAH) are the most ubiquitous and are present in the highest concentrations. Certain exogenous and endogenous factors significantly modify the biologic action of carcinogenic hydrocarbons. Exogenous factors includes (1) the simultaneous presence and action of anticarcinogenic agents in the environment, (2) their occurrence in a physical state compatible with inhalation and deposition in the respiratory tract, and (3) the presence of factors modifying the host response, particularly in relation to the normal physiologic defenses. The endogenous factors include: (1) the vehicle serving the carcinogenic agents as it affects persistence at site of entry and rate of systemic distribution, (2) the rate of metabolism in the hepatobiliary system, and (3) the existence of anatomic or metabolic abnormalities modifying the tissue response. The metabolism of carcinogenic P AH is, in the truest sense, a pharmacologic detoxification process since the metabolites are either weakly or, as is more common, wholly noncarcinogenic. This suggests that carcinogenic PAH, as they occur in the environment, are the proximate carcinogens. The complexity of the carcinogenic process is emphasized by the multiplicity of factors, many of them noncarcinogenic in themselves, that are concerned with the pathogenesis of neoplastic disease.