Oxidative damage to mitochondria in normal and cancer tissues, and its modulation

• Published in: Toxicology (Amsterdam) Vol. 155; no. 1; pp. 73 - 82
• Main Authors: Kamat, J.P., Devasagayam, T.P.A.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 30.11.2000
• Subjects: Animals; Antioxidants - pharmacology; Ascites - metabolism; Ascites tumor; Brain - drug effects; Brain - metabolism; Brain - radiation effects; Caffeine; Caffeine - pharmacology; Gamma Rays; Male; Mitochondria; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Mitochondria, Liver - radiation effects; Niacinamide - pharmacology; Nicotinamide; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Oxidative Stress - radiation effects; oxygen; Palm Oil; Photosensitizing Agents - pharmacology; Plant Oils - pharmacology; Porphyrins; Porphyrins - pharmacology; Pulse Radiolysis; Rats; Rats, Wistar; Sarcoma 180 - metabolism; Tocotrienols; Vitamin E - analogs & derivatives; Vitamin E - pharmacology; Oxidative stress; Mitochondria; Ascites tumor; Nicotinamide; Tocotrienols; Caffeine; Porphyrins
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(00)00279-1

Cellular damage induced by reactive oxygen species (ROS) in normal tissues has been implicated in the etiology of several human ailments. Among the subcellular organelles, damage to mitochondria is considered crucial and can lead to cytotoxicity and cell death. However, the same damage, if it is selectively induced in cancer tissues can lead to its cure. Hence analyzing the mechanisms of such damage and its modulation may result in better prevention or cure. Using mitochondria derived from rat brain/liver as well as sarcoma 180 ascites cells, we have examined the mechanisms of damage to lipid, as assessed by different products of lipid peroxidation and to proteins, as determined by loss of enzyme activity and protein oxidation. Mechanisms involved, in terms of scavenging of ROS have been determined using pulse radiolysis for hydroxyl radical and histidine destruction assay for singlet oxygen. Various ROS were generated using γ-radiation, photosensitization etc. under different conditions. Some novel porphyrins, with potential uses in photodynamic therapy also were used as photosensitizers. Our study shows that ROS can induce significant oxidative damage in mitochondria from both normal and tumor tissues and this can be inhibited by natural antioxidants like tocotrienols, nicotinamide and caffeine. Damage, on the other hand, can be enhanced by deuteration of the buffer and oxygenation. Our results hence demonstrated that mitochondria were sensitive to damage by ROS and its modulation may have potential uses in prevention of the disease in normal tissues; if damage can be selectively induced in tumor, it can lead to its regression.