The Role of Initiating and Promoting Properties in Aromatic Amine Carcinogenesis
Investigations as to the metabolism of carcinogenic aromatic amines have been fundamental in establishing the concept that ultimate reactive electrophiles are responsible for the damage of critical cellular macromolecules and that the DNA-lesions thus produced represent a key event in the generation of tumors1. Putative promutagenic DNA-adducts have been identified in many cases and attempts have been made to correlate the extent of formation and the persistence of such adducts with the carcinogenic potency of the parent amine. Although the basic principle has been confirmed in many instances, the correlations of genotoxic effects of aromatic amines with tumor formation, particularly with tissue-specific tumors were not satisfactory2. For these poor correlations many reasons can be envisaged, one of which is related to the multistage concept of carcinogenesis. According to this concept, irreversible genotoxic effects may well correlate with initiation but not necessarily with the end point tumor which is reached only via a multistep process in which some of the steps could be independent of the early DNA-damaging events.
KeywordsAromatic Amine Genotoxic Effect Oxidize Glutathione Ornithine Decarboxylase Carcinogenic Potency
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