US EPA

1254165 

Journal Article 

Review 

Metabolism of polycyclic aromatic hydrocarbons: etiologic role in carcinogenesis 

Pelkonen, O; Nebert, DW 

1982 

1 

Pharmacological Reviews
ISSN: 0031-6997
EISSN: 1521-0081 

34 

2 

189-222 

English 

6287505 

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0020303079&partnerID=40&md5=f47ef07739ea196eb208099ba6e1953c
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One of the most useful theories to explain some mechanistic aspects of chemical carcinogenesis is the theory of toxification, i.e. the formation of reactive metabolites by enzymes and the covalent linkage of these activated intermediates with cellular macromolecules to initiate the carcinogenic process. With this theory as a background, the authors examine the formation of reactive polycyclic hydrocarbon intermediates and factors affecting their interactions with DNA, RNA, and proteins. They have surveyed the literature concerning the effects of covalent binding of such reactive intermediates on the structure and function of biological macromolecules. They summarize some studies about possible correlations between the binding of these chemicals to DNA and their mutagenicity and carcinogenicity. Although these kinds of correlative studies cannot prove that DNA is the critical target for the carcinogenic action of chemicals, positive correlations at least do not refute this hypothesis. During recent years, important experimental advances have revolutionized the study of the interactions of polycyclic hydrocarbons with macromolecules. First, the availability of compounds of high specific radioactivity has increased the sensitivity of detecting minute amounts of carcinogens bound to nucleic acids. Second, many different metabolites have been synthesized. Third, analytical instrumentation and methods for measuring specific nucleoside-hydrocarbon adducts and for measuring biochemical and biological activity of metabolites have been improved.