Covalent binding to proteins as a mechanism of chemical toxicity.
The capacity of chemicals to interact covalently with cellular macromolecules in in vitro systems was exploited to elucidate the structure of secondary metabolites, namely arene oxide derivatives, in the biotransformation of styrene. Covalent binding to proteins was also determined to check the presence and activity of enzymatic systems in subcellular compartments other than microsomes, e.g., nuclei. In experiments with cyclophosphamide as substrate it was shown that nuclear enzymatic activities might well be responsible for drug covalent binding to DNA.
D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity; D055598:Chemical Phenomena; D002621:Chemistry; D003520:Cyclophosphamide / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D064420:Drug-Related Side Effects and Adverse Reactions; D008862:Microsomes, Liver / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism
D002273:Carcinogens; D004364:Pharmaceutical Preparations; D003520:Cyclophosphamide; D004247:DNA