Metabolic activation of chemical carcinogens.

Abstract

Ideally the end result may differ, but there are similarities between the metabolic pathways of chemical carcinogens and drugs, for both are xenobiotics or foreign substances. Furthermore, certain drugs may increase the risk of a possible carcinogenic effect after long-term administration. In these cases judicious consideration of the risk versus the benefit to the patient is necessary. Drugs more likely to bear this hazard are those used to treat neoplastic or autoimmune diseases, situations where the benefit outweighs future risks. An early example of this type drag was chlornaphazine which eventually led to bladder tumors in the patients, understandable because of its 2-naphthylamine skeleton [1]. Chlornaphazine and other alkylating compounds represent primary or reactive carcinogens which can interact with cellular constituents as such (fig. 1) [2]. Despite the presence of alkylating groups in the widely used cyclophosphamide, this drug apparently does not react as such. Metabolism through 4-hydroxycyclophosphamide and aldophosphamide affords phosphoramide mustard [3, 4] which can form adducts with nucleosides [5]. Thus the cyclophosphamide metabolites act as transport forms of the ultimate cytotoxic metabolite [4].KeywordsPolycyclic Aromatic HydrocarbonAromatic AmineCarcinogenic EffectChemical CarcinogenCellular MacromoleculeThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.