In vivo covalent binding of organic chemicals to DNA as a quantitative indicator in the process of chemical carcinogenesis.
The covalent binding of chemical carcinogens to DNA of mammalian organs is expressed per unit dose, and a 'Covalent-Binding Index', CBI, is defined. CBI for various carcinogens span over 6 orders of magnitude. A similar range is observed for the carcinogenic potency in long-term bioassays on carcinogenicity. For the assessment of a risk from exposure to a carcinogen, the total DNA dmaage can be estimated if the actual dose is also accounted for. A detailed description is given for planning and performing a DNA-binding assay. A complete literature survey on DNA binding in vivo (83 compounds) is given with a calculation of CBI, where possible, 153 compounds are listed where a covalent binding to any biological macromolecule has been shown in vivo or in vitro. Recent, so far unpublished findings with aflatoxin M1, macromolecule-bound aflatoxin B1, diethylstilbestrol, and 1,2-epithiobutyronitrile are included. A comparison of CBI for rat-liver DNA with hepatocarcinogenic potency reveals a surprisingly good quantitative correlation. Refinements for a DNA-binding assay are proposed. Possibilites and limitations in the use of DNA binding in chemical carcinogenesis are discussed extensively.
D000336:Aerosols; D000818:Animals; D001417:Background Radiation; D002273:Carcinogens / Q000008:administration & dosage / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair / Q000187:drug effects; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005821:Genetic Techniques; D006801:Humans; D007267:Injections; D008099:Liver / Q000378:metabolism; D046911:Macromolecular Substances; D008433:Mathematics; D012016:Reference Values; D013329:Structure-Activity Relationship; D013997:Time Factors
D000336:Aerosols; D002273:Carcinogens; D046911:Macromolecular Substances; D004247:DNA