A critical factor in mutagenesis is cell division. When the cell divides, an unrepaired DNA lesion can give rise to a mutation. Thus an important factor in mutagenesis, and therefore carcinogenesis, is the cell division rate in the precursors of tumor cells. Stem cells are important as precursor cells in cancer because they are not on their way to being discarded. Increasing their cell division rate would increase mutation. As expected, there is little cancer in non-dividing cells. Such diverse agents as chronic infection high levels of particular hormones, or chemicals at doses that cause cell death result in increased cell division and therefore an increased risk for cancer.
Oxidants form one important class of agents that stimulate cell division. This may be related to the stimulation of cell division that occurs during the inflammatory process accompanying wound healing. Antioxidants therefore can decrease mutagenesis, and thus carcinogenesis, in two ways:
by decreasing oxidative DNA damage and by decreasing cell division. Of great interest is the understanding of mechanisms by which tocopherol and carotenoids can prevent cell division
There is an increasing literature on the protective role of dietary tocopherol, ascorbate, and ß-carotene in lowering the incidence of a wide variety of human cancer.
Antioxidants can counteract the induction of cancer in rodents by a variety of carcinogens. Two of the major causes of cancer, cigarette smoke and chronic inflammation, both appear to involve oxidants in their mechanism of action.
Almost all of the epidemiological studies that examined the relation between Antioxidant levels and cigarette-induced lung cancer showed a statistically significant protective effect of Antioxidants.
Antioxidants inhibit much of the pathology of cigarette smoke in rodents.
Inflammatory reactions release large amounts of NO, a radical, nitrosating agent, and indirect mutagenic oxidant. Ascorbate inhibits nitrosation under physiological conditions.
Antioxidants help to protect against the carcinogenic effects of chronic inflammation, as discussed above.
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Showing posts with label chronic inflammation. Show all posts
Showing posts with label chronic inflammation. Show all posts
Monday, February 11, 2008
Thursday, February 7, 2008
Sources and Effects of Oxidants
Four endogenous sources appear to account for most of the oxidants produced by cells:
1) As a consequence of normal aerobic respiration, mitochondria consume molecular oxygen, reducing it by sequential steps to produce H20. Inevitable by-products of this process, as stated above, are O2.-, H202, and .OH. About l012 oxygen molecules are processed by each rat cell daily, and the leakage of partially reduced oxygen molecules is about 2%, yielding about 2x1010 superoxide and hydrogen peroxide molecules per cell per day.
2) Phagocytic cells destroy bacteria or virus-infected cells with an oxidative burst of NO, O2.-, H2O2, and [[macron]]OCl. Chronic infection by viruses, bacteria, or parasites, results in a chronic phagocytic activity and consequent chronic inflammation, which is a major risk factor for cancer. Chronic infections are particularly prevalent in third world countries.
3) Peroxisomes, which are organelles responsible for degrading fatty acids and other molecules, produce H202 as a byproduct, which is then degraded by catalase. Evidence suggests that, under certain conditions, some of the peroxide escapes degradation, resulting in its release into other compartments of the cell and in increased oxidative DNA damage.
4) Cytochrome P450 enzymes in animals constitute one of the primary defense systems against natural toxic chemicals from plants, the major source of dietary toxins. The induction of these enzymes, prevent acute toxic effects from foreign chemicals, but also results in oxidant by-products that damage DNA (Park, J.-Y. K. and Ames, B.N., unpublished).
Click here for more about Glutathione and its benefits to our body.
Three exogenous sources may significantly increase the large endogenous oxidant load.
1) The oxides of nitrogen (NOx) in cigarette smoke (about 1000 ppm) cause oxidation of macromolecules, and deplete antioxidant levels. This is likely to contribute significantly to the pathology of smoking. Smoking is a risk factor for heart disease as well as a wide variety of cancers in addition to lung cancer.
2) Iron (and copper) salts promote the generation of oxidizing radicals from peroxides (Fenton chemistry). Men who absorb significantly more than normal amounts of dietary iron due to a genetic defect (hemochromatosis disease) are at an increased risk for both cancer and heart disease. It has therefore been argued that too much dietary copper or iron, particularly heme iron (which is high in meat), is a risk factor for cardiovascular disease and cancer in normal men
3) Normal diets contain plant food with large amounts of natural phenolic compounds, such as chlorogenic and caffeic acid, that may generate oxidants by redox cycling .
Click here for more about Glutathione and its benefits to our body.
1) As a consequence of normal aerobic respiration, mitochondria consume molecular oxygen, reducing it by sequential steps to produce H20. Inevitable by-products of this process, as stated above, are O2.-, H202, and .OH. About l012 oxygen molecules are processed by each rat cell daily, and the leakage of partially reduced oxygen molecules is about 2%, yielding about 2x1010 superoxide and hydrogen peroxide molecules per cell per day.
2) Phagocytic cells destroy bacteria or virus-infected cells with an oxidative burst of NO, O2.-, H2O2, and [[macron]]OCl. Chronic infection by viruses, bacteria, or parasites, results in a chronic phagocytic activity and consequent chronic inflammation, which is a major risk factor for cancer. Chronic infections are particularly prevalent in third world countries.
3) Peroxisomes, which are organelles responsible for degrading fatty acids and other molecules, produce H202 as a byproduct, which is then degraded by catalase. Evidence suggests that, under certain conditions, some of the peroxide escapes degradation, resulting in its release into other compartments of the cell and in increased oxidative DNA damage.
4) Cytochrome P450 enzymes in animals constitute one of the primary defense systems against natural toxic chemicals from plants, the major source of dietary toxins. The induction of these enzymes, prevent acute toxic effects from foreign chemicals, but also results in oxidant by-products that damage DNA (Park, J.-Y. K. and Ames, B.N., unpublished).
Click here for more about Glutathione and its benefits to our body.
Three exogenous sources may significantly increase the large endogenous oxidant load.
1) The oxides of nitrogen (NOx) in cigarette smoke (about 1000 ppm) cause oxidation of macromolecules, and deplete antioxidant levels. This is likely to contribute significantly to the pathology of smoking. Smoking is a risk factor for heart disease as well as a wide variety of cancers in addition to lung cancer.
2) Iron (and copper) salts promote the generation of oxidizing radicals from peroxides (Fenton chemistry). Men who absorb significantly more than normal amounts of dietary iron due to a genetic defect (hemochromatosis disease) are at an increased risk for both cancer and heart disease. It has therefore been argued that too much dietary copper or iron, particularly heme iron (which is high in meat), is a risk factor for cardiovascular disease and cancer in normal men
3) Normal diets contain plant food with large amounts of natural phenolic compounds, such as chlorogenic and caffeic acid, that may generate oxidants by redox cycling .
Click here for more about Glutathione and its benefits to our body.
Wednesday, February 6, 2008
Inflammation, Free Radicals, and Cytokines
Although acute Inflammation is an important immune system response, chronic inflammation has also been linked to many diseases, including heart disease. Besides the pro-Inflammation cytokines, Inflammation may be related to the overproduction of free radicals (Janeway CA et al 1999).
A free radical is an atom or group of atoms (i.e., a molecule) with unpaired electrons. Free radicals are extremely unstable and react easily with other molecules, thereby changing their chemical composition. Oxygen is especially susceptible to free radical formation. The free radicals derived from oxygen are known as reactive oxygen species, or oxidants.
When the body has increased levels of reactive oxygen species (i.e., when it is experiencing oxidative stress), widespread damage may result. At high concentrations free radicals can damage fats, proteins, and nucleic acids. They can also cause cell death, gene mutations, and cancer ( Moslen MT 1994). Several diseases may be the result of cellular and genetic damage caused by free radicals, including several immune disorders ( Moslen MT 1994).
In order to reduce the damage caused by elevated free radicals and cytokines (which are both part of the natural immune system), the body fights back by producing antioxidants and hormones such as cortisol to suppress the immune system (Grimble RF 1996). Antioxidants are valuable because they pair with unstable free radicals, thereby limiting the damage free radicals can inflict on other cells.
Click here for more about Glutathione and its benefits to our body.
A free radical is an atom or group of atoms (i.e., a molecule) with unpaired electrons. Free radicals are extremely unstable and react easily with other molecules, thereby changing their chemical composition. Oxygen is especially susceptible to free radical formation. The free radicals derived from oxygen are known as reactive oxygen species, or oxidants.
When the body has increased levels of reactive oxygen species (i.e., when it is experiencing oxidative stress), widespread damage may result. At high concentrations free radicals can damage fats, proteins, and nucleic acids. They can also cause cell death, gene mutations, and cancer ( Moslen MT 1994). Several diseases may be the result of cellular and genetic damage caused by free radicals, including several immune disorders ( Moslen MT 1994).
In order to reduce the damage caused by elevated free radicals and cytokines (which are both part of the natural immune system), the body fights back by producing antioxidants and hormones such as cortisol to suppress the immune system (Grimble RF 1996). Antioxidants are valuable because they pair with unstable free radicals, thereby limiting the damage free radicals can inflict on other cells.
Click here for more about Glutathione and its benefits to our body.
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