Electronic aspects of the interactions between the carcinogens and possible cellular sites of their activity

Abstract

In aromatic hydrocarbons the carcinogenic activity may be quantitatively correlated with the electronic properties of specific regions: the so-called “K” and “L” regions. In order to be carcinogenic the molecules must possess a “reactive” K region (double bond) and an “unreactive” L region (para positions). The correlation implies that the interaction leading to carcinogenesis must occur through the K region and involve a strong chemical binding of the type of an addition reaction, possibly subject to steric hindrance. No correlation exists between carcinogenicity of hydrocarbons and their electron transfer properties. The interactions of carcinogenic hydrocarbons with proteins yield results in striking agreement with the theoretical inferences. They indicate the formation of a strong chemical bond between the carcinogens and proteins, through the K region, the reaction involved being an addition. The formation of the complex correlates with the existence of the activity and with its potency. The interactions with the nucleic acids, less explored, may involve hydrophobic and charge transfer forces. In agreement with theoretical predictions this binding is not specific with respect to carcinogens. In other groups of carcinogens (azo-dyes, aromatic amines, aminofluorene), the situation is to a large extent similar: significant interactions with proteins, ill-defined interactions with the nucleic acids. The alkylating agents, on the other hand, interact significantly with the nucleic acids. With the possible exception of these last agents, the interaction of molecules with proteins seems to be more directly correlated with the appearance of cancer than their interaction with the nucleic acids.