Biomarkers of apoptosis: Release of cytochrome c, activation of caspase-3,induction of 8-hydroxy-2 '-deoxyguanosine, increased 3-nitrotyrosine, and alteration of p53 gene

Biomarkers rely on biochemical, histological, morphological, and physiologi cal changes in whole organisms. Their use is becoming an important tool to examine changes at cellular and molecular levels, especially in nucleic aci ds and proteins. Biomarkers are used to measure exposure to a toxic agent, to detect severity of any toxic response, and to predict the possible outco me. Information on the mechanisms of action of toxicants can allow the deve lopment of potential biomarkers of effect and thus improvement of the risk assessment processes. Use of biomarkers as a tool to predict induction of a poptosis allows identification of biological signs that may indicate increa sed risk for disease. In cells undergoing apoptosis, the release of cytochr ome c from the mitochondria to the cytoplasm and the activation of caspase- 3, a key enzyme to execution stage of apoptotic pathway. have been studied as biomarkers of cell death (apoptosis). Products of DNA fragmentation that either accumulate in the cellular tissues or are excreted in the urine are useful markers of DNA damage. The induction level of urinary or cellular l evel of 8-hydroxy-2-deoxyguanosine and 3-nitrotyrosine has been used as a m arker to measure extent of DNA oxidative damage. Furthermore, alteration or overexpression of the p53 gene was considered an indication of apoptosis. This article reviews some of the aspects of biomarkers of apoptosis, indica ting relevance of their uses to predict apoptosis following exposure to env ironmental toxicants.