ABSTRACT
Cellular genomes are continually subjected to endogenous and environmentally induced structural alterations, damage that can manifest itself as gross chromosomal abnormalities resulting in cell death. Although it has proven difficult to classify cell death based on the morphology of dying cells and on the DNA fragmentation or damages, two distinct patterns of cell death have been identified. These have been termed necrosis and apoptosis [1]. Mammalian cell death can be induced through chromosomal DNA damage by oxidative stresses such as ionizing and ultra violet (UV) radiation, anticancer drugs, and various DNAadduct-inducing substances. Under oxidative stress, reactive oxygen species (ROS) such as hydroxyl radicals (•OH), superoxide anions (O2•), and hydrogen peroxide (H2O2) have been shown to damage chromosomal DNA and other cellular components, resulting in DNA degradation, protein denaturation, and lipid peroxidation. However, the mechanisms behind these cellular effects are rather complex and are not yet fully understood. DNA damage induced by oxygen radicals occurs by oxidative nucleic acid base modification and scission of DNA strands, the latter resulting in single-and double-strand breaks [2]. Some agents producing ROS induce cell death, including apoptosis, and cause lipid peroxidation and DNA damage [3]. However, the implications of lipid peroxidation in ROS-induced DNA damage remain to be elucidated. Furthermore, it is not clear whether ROS are a part of the signal transduction cascade triggered by various inducers of apoptosis or whether they are generated in a parallel pathway that can independently trigger apoptosis. It is important, therefore, to distinguish between ROS molecules involved in such signaling pathways and those that mediate general cellular damage, including giant DNA and high-molecularweight DNA fragmentation. These DNA fragmentations in chromatin, estimated by size and emerging time of the fragments, might reveal either apoptosis or necrosis.
