By R. J. Roberts
Apoptosis in Toxicology is the 1st ebook to target the molecular legislation of apoptosis with specific emphasis on toxicant motion. telephone survival signalling and its perturbation is addressed on the genetic and biochemical point, together with key survival and loss of life genes, survival signalling, dedication to apoptosis and recruitment of the initiator and executioner caspases. Emphasis is given to the function apoptosis performs within the motion of toxicants within the mind, the immune method, the reproductive organs, the kidney and the liver. the facility of gear to manage apoptosis both as a objective or as an antagonistic impact is mentioned with specific connection with melanoma chemotherapy. the various tools that may be hired to quantify apoptosis are in comparison and their program to diverse tissues is mentioned. This well timed and complete quantity has been written by way of major professionals and lively researchers of their respective fields. it's going to have wide entice toxicologists, physicians and biologists throughout many disciplines.
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The fact that an anti-metabolite can induce apoptosis in non-cycling cells is surprising but recent studies have shown that fludarabine is phosphorylated to 2CdATP which then activates caspases by interacting with Apaf-1 and cytochrome c. , 1998). These results demonstrate that caspase activation and cell death can be induced directly and perhaps explains why these compounds are so toxic. 5 SUMMARY are tightly controlled. Precise metabolic pathways exist to activate the caspases, which then dismantle the cell.
The toxicological consequences and mechanisms of this caspase activation and its inhibition are considered in this chapter. The activation of the caspases seems to represent an all or nothing, one way process concluding in life or death of the cell. Thus, the possible toxicological consequences of interference with caspase activity are great and could be derived from either inappropriate activation or inhibition of the caspases. To address this, the enzymology of the caspase enzymes is discussed in the next section followed by a final section describing modulation of caspase activity and the possible consequences of activating or inhibiting caspases.
The major controlling factors for apoptosis appear to be upstream of caspase activation (see Chapter 1 for a discussion of commitment and execution). However, the existence of viral inhibitors suggest that the caspase-inhibited cell remains sufficiently viable for the virus to replicate itself even though the cell death 28 ! TOXICOLOGICAL CONSEQUENCES OF CASPASE INHIBITION commitment status of the cell has not changed. It is not clear whether cell death has been temporarily delayed or abolished although there is some evidence that caspase inhibited cells still have clonogenic potential (Longthorne and Williams, 1997).
Apoptosis in Toxicology by R. J. Roberts