[Chemical carcinogens and DNA, covalent binding and chemical modifications].
Chemical carcinogenic agents are usually metabolized into final metabolites susceptible to be DNA bound to form adducts. They may also modify DNA bases. Binding may be studied in vitro in the presence of an enzyme system causing the formation of final metabolites or in vivo. Because of the small amount of adducts formed in vivo, they can only be visualized with radioactive compounds or with a 32P marking technique after DNA hydrolysis. A limit of detection of adduct for 10(8) nucleotides has thus been reached for polycyclic compounds. The covalent binding index enables to quantify this binding. The consequences of DNA alterations vary according to the substitutes. In the case of acetyl-aminofluorene, they lead to mutations by shifting of the reading frame (frameshift). Alkylations lead to inaccurate pairing causing pin point mutations or depurinations.
D002273:Carcinogens / Q000378:metabolism* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D013329:Structure-Activity Relationship
D002273:Carcinogens; D010761:Phosphorus Radioisotopes; D004247:DNA
Cancérogènes chimiques et ADN, liaison covalente et modifications chimiques.