DNA cross-linking is seen with many bifunctional electrophiles, i.e., compounds with two separate electrophilic centers. Depending upon the geometry of the atoms in the DNA bases that react, intra- and interstrand DNA cross-links result. These are generally very detrimental to the progress of DNA polymerases. Thus, some of these compounds are used to treat cancers, in that they have the effect of slowing the growth of rapidly dividing tumor cells, in which DNA synthesis is robust. However, DNA cross-linking can also cause miscoding and mutations. Another phenomenon is DNA-protein cross-linking, which has been observed but is not well understood. Enzymes are present in cells to repair DNA cross-links. However, these repair systems can negate the effects of drugs used to treat tumors, and some therapy regimens include blocking the repair.
Cross-linking is one of the most disruptive events that can occur with DNA, particularly interstrand cross-linking and...
KeywordsFormaldehyde Toxicity Glutathione Adduct Thiol
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