Genotoxic stress apoptosis activation

Genotoxic stress, as manifested by, e. g., the formation of DNA adducts and DNA strand breaks, activates p53 mostly via DNA damage checkpoints. In this process, the cell cycle is arrested and timeis gained for repair of the damaged DNA, or alternatively, the cell is driven into apoptosis. It is the main purpose of this control to prevent replication of damaged DNA, which is a potentially mutagenic process. The links between DNA damage and p5 3 activation are summarized schematically in Fig. 14.13. 

In somatic cells, p53 is stabilised and activated upon genotoxic stress which can lead to cell cycle arrest, senescence or apoptosis. Upon stress p53 activates the transcription of many genes such as p21, Mdm2, Noxa and Puma that mediate the cell cycle arrest, senescence and apoptotic processes. Apoptosis can also be induced in a p53-dependent but transcription-independent manner by targeting the mitochondria thereby inducing cytochrome-C release (Zhao and Xu, 2010). 

C. L. Crowley-Weber, K. Dvorakova, C. Crowley, H. Bernstein, C. Bernstein, H. Garewal and C. M. Payne, Nicotine increases oxidative stress, activates NF-kappaB and GRP78, induces apoptosis and sensitizes cells to genotoxic/xenobiotic stresses by a multiple stress inducer, deoxy-cholate relevance to colon carcinogenesis, Chem. Biol. Interact., 2003, 145(1), 53. 

Apoptosis is induced by a variety of stimuli, such as genotoxic compounds, tumor necrosis factor, Eas ligand, and various environmental stresses. Despite the diversity of apoptosis-inducing agents, numerous experiments indicate that signals leading to the activation of members of the intracellular cysteine protease family, for instance, the caspase, may play a pivotal role in the initiation and execution of apoptosis induced by various stimuli. ... 

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