![]() These signaling routes can lead to transcriptional induction of target genes that could promote proliferation or confer apoptosis resistance to exposed cells. Reactive oxygen species: from health to disease Upon reaction with electrons, oxygen is transformed into reactive oxygen species (ROS). Besides causing DNA damage, ROS further induce multiple intracellular signaling pathways, notably NF-kappa B, JNK/SAPK/p38, as well as Erk/MAPK. Increased ROS generation often has been linked to DNA damage that can lead to mutations and may, therefore, play an important role in the initiation and progression of multistage carcinogenesis. ROS are also generated due to induction of various cytochrome P450 isoenzymes during detoxification of chemical carcinogens. Trace metals generate reactive oxygen species (ROS) depending on their ability to lose electrons and catalyze Haber Weiss and Fenton reactions. Overview Aerobic organisms, which derive their energy from the reduction of oxygen, are susceptible to the damaging actions of the small amounts of O 2-, OH and H 2 O 2 that inevitably form during the metabolism of oxygen, especially in the reduction of oxygen by the electron transfer system of mitochondria. Trace metals and organic xenobiotics are typical classes of environmental pollutants with prooxidant effects. Enzymes and subcellular compartments that typically produce ROS are associated with metabolic regulation, and diseases associated with metabolic dysfunction may be influenced by changes in redox balance. The biochemical modes of action for nongenotoxic carcinogens are diverse, one example of which is induction of oxidative stress. Reactive oxygen species (ROS) are well known for their role in mediating both physiological and pathophysiological signal transduction. There is, however, a group of carcinogens that induce cancer via nongenotoxic mechanisms. In the majority of instances, chemical carcinogens, directly or after xenobiotic metabolism, induce DNA damage and act in a 'genotoxic' manner. Chemical carcinogens can alter any of these processes to induce their carcinogenic effects. It is well established that cancer is a multi-step process which involves initiation, promotion and progression. ![]()
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