Jp. Kamat et Tpa. Devasagayam, Oxidative damage to mitochondria in normal and cancer tissues, and its modulation, TOXICOLOGY, 155(1-3), 2000, pp. 73-82
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.