Are carcinogens electron acceptors? A novel hypothesis.

U S Vishal Rao, Gururaj Arakeri, Anand Subash, M Venkatesh, Peter A Brennan

Medical hypotheses 2020 Nov

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Carcinogens play a key role in cancer initiation. Conventional theories support the concept of genetic changes inducing tumorigenesis through proteomics and metabolomics which lead to cancer development. Current research provides evidence that metabolic genes may be altered long before mutation of tumour suppressor genes, strongly suggesting that metabolic changes may be preceding the changes seen at a genetic level. Since cancer has long been known to occur through gene regulation, an impaired cellular respiration without utilizing mitochondrial function has been an area of active interest. We hypothesize the activity of carcinogens as electron acceptors to disrupt the normal glycolysis cycle happening in a cell by acting as positive ligands. The continuous restoration of NAD+ to cytosol by oxidation of NADH with carcinogen as electron acceptor creates a metabolic pathway to assist in the carcinogenic process. This metabolic pathway continues through an adaptive process, supplemented by pyruvate converting to lactate providing a constant pool of NAD+ to continue the glycolytic pathway. We also hypothesize that carcinogenesis occurs as a precursor to metabolic stress which may promote altered genetic and protein expression causing aberrant epigenetic and cell signaling pathways. Copyright © 2020 Elsevier Ltd. All rights reserved.

Citation

U S Vishal Rao, Gururaj Arakeri, Anand Subash, M Venkatesh, Peter A Brennan. Are carcinogens electron acceptors? A novel hypothesis. Medical hypotheses. 2020 Nov;144:110235