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

Cellular damage induced by reactive oxygen species (ROS) in normal tissues has been implicated in the etiology of several human ailments. Among the su bcellular organelles, damage to mitochondria is considered crucial and can lead to cytotoxicity and cell death. However, the same damage, if it is sel ectively induced in cancer tissues can lead to its cure. Hence analyzing th e mechanisms of such damage and its modulation may result in better prevent ion or cure. Using mitochondria derived from rat brain/liver as well as sar coma 180 ascites cells, we have examined the mechanisms of damage to lipid, as assessed by different products of lipid peroxidation and to proteins, a s determined by loss of enzyme activity and protein oxidation. Mechanisms i nvolved, in terms of scavenging of ROS have been determined using pulse rad iolysis for hydroxyl radical and histidine destruction assay for singlet ox ygen. Various ROS were generated using gamma -radiation, photosensitization etc. under different conditions. Some novel porphyrins, with potential use s in photodynamic therapy also were used as photosensitizers. Our study sho ws that ROS can induce significant oxidative damage in mitochondria from bo th normal and tumor tissues and this can be inhibited by natural antioxidan ts 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 it s 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. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.