Folic Acid Role in Mutagenesis, Carcinogenesis, Prevention and Treatment of Cancer

ABSTRACT

In 1987 we have published a hypothesis for the role of folic acid in the cancer prevention. Many research data, concerning the involvement of folate in the aetiology of cancer, accumulated since 1987 till now, support our hypothesis. Nowadays, the important role of folic acid in the normal cell metabolism, especially in the DNA synthesis and gene expression, and the role of folate deficiency in the development of some pathological processes, including cancer, are considered to be proved. In the present article we show the suppressive effect of folic and tetrahydrofolic acid on the DNA alkylation with a spin-labeled (containing nitroxyl radical) hydrazine mustard antitumor agent, by the electron spin resonance (ESR) method in vitro. We follow briefly the normal biological functions of folic acid and the established molecular effects of folate deficiency. Basing on our and other authors studies, including quantum biochemical ones, on the folic acid and other low molecular weight nucleophilic compounds in the cell we connect the folate depletion with the strong nucleophilic properties of hydrogenated folates, especially tetrahydrofolate, that determinate it as one of the first targets of the electrophilic attack of agents with carcinogenic potential, including the reactive oxygen species. We consider that an unified theory for mutagenesis, carcinogenesis, cancer prevention and therapy putting the folate and tetrahydrofolate in the center of the events, has been created.