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Week_4_-_Chemical_Carcinogens - Week 4 Chemical Carcinogens...

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Week 4 - Chemical Carcinogens Although there is continued debate of the molecular mechanisms involved in carcinogenesis, there is no debate over the fact that certain chemicals can act as carcinogens. Evidence for this comes from both epidemiological and experimental animal studies. Carcinogens that have the ability to bind to and alter the structure of DNA are generally called genotoxic (or genetic ) carcinogens , while carcinogens that bind to and affect other cellular targets are known as epigenetic carcinogens . Some compounds appear to be intrinsically carcinogenic, whereas others must undergo bioactivation to produce reactive metabolites. Although the many substances identified as chemical carcinogens have a very broad range of structures with no obvious unifying features, they can be classified into two broad categories: direct-acting and indirect-acting. Structures of some chemical carcinogens (figure legend). Direct-acting carcinogens are highly electrophilic compounds that can react with DNA. Indirect-acting carcinogens must be metabolized before they can react with DNA. All these chemicals can act as mutagens. Direct-acting carcinogens, of which there are only a few, are reactive electrophiles (compounds that seek out and react with negatively charged centers in other compounds). By chemically reacting with nitrogen and oxygen atoms in DNA, these compounds modify certain nucleotides so as to distort the normal pattern of base pairing.
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If these modified nucleotides were not repaired, they would allow an incorrect nucleotide to be incorporated during replication. Indirect-acting carcinogens generally are unreactive, water-insoluble compounds. They can act as potent cancer inducers only after conversion to ultimate carcinogens by introduction of electrophilic centers. Such metabolic activation of carcinogens is carried out by enzymes that are normal body constituents. In animals, activation of indirect- acting carcinogens (bioactivation) often is carried out by liver enzymes that normally function to detoxify noxious chemicals (e.g., therapeutic drugs, insecticides, polycyclic
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Week_4_-_Chemical_Carcinogens - Week 4 Chemical Carcinogens...

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