Researches on chemical carcinogens and mechanism of chemical carcinogenesis. Di-region theory--a quantitative molecular orbital model of carcinogenic activity for polycyclic aromatic hydrocarbons.
In this paper, we prove by perturbational molecular orbital (PMO) theory that with polycyclic aromatic hydrocarbons (PAH) there exist two regions having electrophilic activity, which are the necessary and sufficient condition for its carcinogenic activity. We are the first to obtain a quantitative equation for the carcinogenic activity of PAH, using the carbonium ion delocalization energies as parameters. By using the equation, the calculated carcinogenic activity is in fair accord with the experiment, and the consistent ratio comes up to 98%. Further study shows that the optimum distance for carcinogenic activity approximates to 2.80 A. This is just the distance between the negative centers in DNA double helix. Therefore, the key step of the carcinogenesis for PAH in vivo is the interstrand cross linkage between the DNA complementary base pair. In terms of this deduction, we suggest that the possible mechanism of chemical carcinogenesis should be a complementary frameshift mutation between the DNA double helix. We name such an idea "di-region theory", which probably might be of general significance for other chemical carcinogenesis.
D002273:Carcinogens / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000378:metabolism; D008956:Models, Chemical; D011083:Polycyclic Compounds / Q000494:pharmacology*; D011789:Quantum Theory; D013329:Structure-Activity Relationship
D002273:Carcinogens; D011083:Polycyclic Compounds; D004247:DNA