Charge Transfer Mechanism for Carcinogenesis by Alkylating and Other Agents
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Bioelectrochemistry and Bioenergetics
This study was undertaken as an outgrowth of the oxy radical-iminium theory of carcinogenesis. A conjugated iminium species is thought to act in certain cases as a charge transfer entity resulting in the generation of oxy radicals which attack DNA. The iminium ion is commonly formed from the purine constituents of nucleic acids via electrophilic attack by alkylating agents. In electrochemical studies, the protonated forms of the purines are used as models for the salts generated in vivo by alkylation. Polarographic and cyclic voltammetry data correlate remarkably well with the current picture relating carcinogenicity with site of alkylation and defect persistence. Other oncogens, e.g., quinones, metals, N-oxypurines, radiation, carbon tetrachloride, 4-nitroquinoline-1-oxide, and inert bodies, are also discussed. The general theory and accompanying experimental results are in keeping with various important facets of the cancer literature. Therefore, a charge transfer mechanism appears reasonable for the cell-transforming process resulting from the action of alkylating and certain other agents.