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

With the help of results on the metabolism and the carcinogenicactivities of polycyclic aromatic hydrocarbons (PAH), the comprehensivemetabolic process in vivo is discussed. It is thought that thecarcinogenic activity exhibited by a PAH is determined by thecompetition between the carcinogenesis and detoxification inwhich it participates. It is suggested that the essential agentof carcinogenesis should be, as a rule, the highest delocalizationenergy (ß unit) of the carbonium ion at the aromaticangular ring (A region), which is obtained by the perturbationalmolecular orbit (PMO) method. Since there are no essential distinctionsin the molecular geometry and delocalization energy states betweentwo carbonium ions of the aromatic angular ring and of the bayregion, the A region can be looked upon as the extended bayregion. On the basis of discussion of the overall metabolism,evaluation of the detoxification efficacy of each kind of thecompeting carcinogenic factors, including the biological factorB and three structural factors of the PAH molecule: K, A andL, 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 thesevalues that the L region plays the most important role in detoxificationprocesses, and the K region plays the least important role.The effect of biological factor B is approximately the sum ofthe K region and the A region. This paper suggests the conceptof a carcinogenic constant. For the PAHs with the same numberof aromatic rings (N), C is a constant. The curve of functionC=f(N), including the extensional line, is an isosceles triangle.The author suggests that it should be called the ‘PyramidRule’. The final form of the quantitative equation is. The values for 50 PAHs which had been tested by animal experiments were calculated. Of these, 92% of thePAHs are in agreement with experiments on carcinogenic activities.