| Popis: |
Publisher Summary The conjugation-dependent bioactivation of foreign compounds for carcinogenesis and toxicity had its origin in research. These investigations concerned primarily the metabolism and carcinogenicity of two compounds: 4-dimethylaminoazobenzene (DAB) and 2-acetylaminofluorene (AAF). The carcinogenic activity of DAB in the rat has been first reported. The long-term objective of the studies was the elucidation of the biochemical mechanisms of action of these carcinogens in the induction of tumors, especially in the liver, in rats after prolonged feeding of these compounds. These studies led to several observations: (1) the covalent binding of carcinogens to the cellular macromolecules of tissues undergoing carcinogenesis, (2) the hepatic microsomal oxidases that metabolize many carcinogens and drugs and the induction of the synthesis of these enzymes in vivo following the administration of many different chemicals, and (3) the activation of many carcinogens by hepatic oxidases and conjugases to form electrophilic ultimate carcinogens that covalently bind to informational macromolecules in cells and initiate the development of carcinogenic, mutagenic, and other toxic lesions. |
