We examined the role of main cell protective mechanisms in retaining the high resistance of ascitic cells (EAC, ZAH) to lipid peroxidation with respect to different stages of tumor-organism metabolic interactions. The following mechanisms were studied: (1) the activity of main EAC enzymatic antioxidants (GSH-Px, SOD); (2) changes in lipid metabolism, especially the content of the main PUFA (linoleic and arachidonic fatty acids) in EAC cells; (3) comparison of intracellular resistance between EAC/ZAH cytoplasmic sections (containing LP-granules or not) to lipid peroxidation (initialized directly by UV-light). We found that the high resistance to lipid peroxidation was typical for cytoplasma sections (without LP-granules) on all stages of tumor development in vivo. The intracellular LP-granules become the main sensitive targets for FR-action, but only in the chronic hypoxia state of EAC/ZAH tumor cells. The latter effect developed in close correlation with the following metabolic interactions: (1) increasing the proportion of PUFA (especially, arachidonic and linoleic acids) transported to EAC tumor cells from host organs and accumulated mainly in tumor LP-granules, and (2) decreasing the alpha-tocopherol content of these hypoxic EAC cells while no activation of the main cell antioxidative enzymes (GSH-Px, SOD) took place. The vitality and high resistance of EAC stationary cells were accompanied by the 'paradoxical' state with great differences between the resistance of the intracellular PUFA-rich granules and other cytoplasmic sections. A similar state was found in stationary ZAH cells. The cell state is in good agreement with the Dormandy's suggestion that PUFA-rich granules can trap reactive radical species preventing their interaction with 'critical' PUFA-membranes.

Natural dicarbonyls, which may be accumulated during oxidative stress in atherosclerosis (e.g. malondialdehyde) or carbonyl stress in diabetes mellitus (glyoxal and methylglyoxal) effectively inhibited the activities of commercial preparations of antioxidant enzymes: catalase, Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and Se-contained glutathione peroxidase from human and bovine erythrocytes and also rat liver glutathione-S-transferase. After incubation of human erythrocytes with 10 mM of each investigated dicarbonyls the decrease of intracellular Cu,Zn-SOD was observed. The decreased activity of erythrocyte Cu,Zn-SOD was also detected in diabetic patients with carbohydrate metabolism disturbance but effective sugar-lowered therapy was accompanied by the increase of this enzyme activity. The increase of erythrocytes activity of Cu,Zn-SOD of diabetic patients theated with metformin (which may utilize methylglyoxal) was higher than in erythrocytase of diabetic patients subjected to traditional therapy.

Free radical oxidation of arachidonic acid with soybean lipoxygenase was accompanied by inhibition of retinal synthesis from beta-carotene catalyzed by enzyme preparation from rabbit intestinal mucosa. Lipoxygenase inhibitor salicylhydroxamic acid and antioxidants suppressing free radical reactions (ethyl gallate, alpha-tocopherol, astaxanthine, and quercetin) promoted conversion of beta-carotene into retinal catalyzed by beta-carotene-15,15'-dioxygenase. These results indicate that lipoperoxides and/or products of their homolysis attenuate enzymatic conversion of beta-carotene and confirm the important role of natural antioxidants in the maintenance of stable vitamin A content in mammals.