Carcinogenesis--a new point of view.
Presented article suggests the novel hypothesis of carcinogenesis, where the key moment for all types (biological, physical, chemical) of carcinogenesis has been discussed. For confirmation of the hypothesis thorough theoretical analysis of the mechanisms of malignant transformation of cells after influence of any type of carcinogens and results of experiments have been presented. Hypothesis highlights are formulated as follows: 1) Covalent bond disorders between S+-methionine and Fe3+ atoms in cytochrome; 2) Electron transport chain blockade with certain ligand after its penetration in cytochrome pocket with further formation of 6th coordination bond between ligand and Fe atom (in one case increase in mitochondrial pH precede-, and in other, it follows electron transport chain blockade in cytochromes); 3) Fe3+ reduction up to Fe2+ leading to blockade of aerobic glycolysis; 4) Decrease in enzyme (Е1-TDP, oxidases etc.) activity due to mitochondrial pH alterations; 5) Production of S-adenosylmethionine owing to lipoic acid amide leading to accumulation of homocysteine in cytoplasm with further penetration in cell nucleus producing DNA mutations; 6) Fe2+ wash-out from cytochrome and its deposition in ferritin.
Oncology National Center, Tbilisi State Medical University, Georgia.
L
L
Gevorkyan
Oncology National Center, Tbilisi State Medical University, Georgia.
K
K
Gambashidze
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D063646:Carcinogenesis / Q000187:drug effects*; D008297:Male; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D010119:Oxythiamine / Q000031:analogs & derivatives*
D010119:Oxythiamine