Direct interception of mutagens and carcinogens by biomolecules.
Five points are emphasized: 1. Chemical interception and mere physical exclusion of mutagens and carcinogens constitute the major means by which mutations in cellular DNA are prevented. DNA repair processes comprise critical, but relatively minor, modes of genetic protection. 2. Disruption of a mutagen-interception defense mechanism can lead to substantial increases in mutagenesis and can preordain sites to eventual tumor formation. 3. Quantitation of the relative contributions of various blocking molecules is often simplified by the fact that protection can be calculated merely through knowledge of the measured concentration of the antimutagen and its rate of reaction with specific mutagens as measured in straightforward in vitro tests. 4. Two recently recognized defensive molecules, carnosine and ergothioneine, are put ++forward as examples of interesting chemical interceptor molecules. 5. Essentially all antimutagens are in fact "double-edged swords." Situations can be artificially constructed that can lead to generation of toxic species from molecules that are normally antimutagens; in isolated cases some of these interactions can be pictured as having deleterious consequences in vivo. This may be one reason why a number of important antimutagens are often sequestered, either in different tissues or by binding to dispensable macromolecules.
Hartman
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Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218.
Hartman
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D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001260:Ataxia Telangiectasia; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D004247:DNA / Q000187:drug effects / Q000235:genetics; D004260:DNA Repair; D004261:DNA Replication / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects
D016588:Anticarcinogenic Agents; D016587:Antimutagenic Agents; D002273:Carcinogens; D009153:Mutagens; D004247:DNA; D005978:Glutathione