Study of the carcinogenic mechanism for polycyclic aromatic hydrocarbons--extended bay region theory and its quantitative model. 1985

L S Yan

With the help of results on the metabolism and the carcinogenic activities of polycyclic aromatic hydrocarbons (PAH), the comprehensive metabolic process in vivo is discussed. It is thought that the carcinogenic activity exhibited by a PAH is determined by the competition between the carcinogenesis and detoxification in which it participates. It is suggested that the essential agent of carcinogenesis should be, as a rule, the highest delocalization energy (beta unit) of the carbonium ion at the aromatic angular ring (A region), which is obtained by the pertubational molecular orbit (PMO) method. Since there are no essential distinctions in the molecular geometry and delocalization energy states between two carbonium ions of the aromatic angular ring and of the bay region, the A region can be looked upon as the extended bay region. On the basis of discussion of the overall metabolism, evaluation of the detoxification efficacy of each kind of the competing carcinogenic factors, including the biological factor B and three structural factors of the PAH molecule: K, A and L, was made. After making necessary approximation, K = 0.228, A = 0.5, L = 1.22 and B = 0.7 are obtained. It can be seen from these values that the L region plays the most important role in detoxification processes, and the K region plays the least important role. The effect of biological factor B is approximately the sum of the K region and the A region. This paper suggests the concept of a carcinogenic constant. For the PAHs with the same number of aromatic rings (N), C is a constant. The curve of function C = f(N), including the extensional line, is an isosceles triangle. The author suggests that it should be called the 'Pyramid Rule'. The final form of the quantitative equation is log R = C[delta E3deloc/(0.7 + 0.228nk + 0.5na + 1.22n1)]. The values for 50 PAHs which had been tested by animal experiments were calculated. Of these, 92% of the PAHs are in agreement with experiments on carcinogenic activities.

UI MeSH Term Description Entries
D008433 Mathematics The deductive study of shape, quantity, and dependence. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Mathematic
D008956 Models, Chemical Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. Chemical Models,Chemical Model,Model, Chemical
D011083 Polycyclic Compounds Compounds which contain two or more rings in their structure. Compounds, Polycyclic
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships

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