Arylamine drugs: genotoxic-carcinogenic activity of NO-derivatives.
This review provides information on arylamine drugs which have been tested for the formation of N-nitroso compounds (NOC) by reacting with nitrite, and on the genotoxic-carcinogenic effects of their nitrosation products. In an extensive search we have found that 109 arylamine drugs were examined for their ability to react with nitrite, and 105 of them (96.3 %) were found to form NOC or in some cases other reactive species. Moreover, 78 arylamine drugs were examined in short-term genotoxicity tests and/or in long-term carcinogenicity assays, either in combination with nitrite or using their nitrosation product; 67 of them (85.9 %) have been found to give at least one positive response. Only a small fraction, the 19.1 % of theoretically nitrosatable arylamine drugs, has been examined for the possible formation of genotoxic-carcinogenic NOC, guidelines for genotoxicity testing of pharmaceuticals do not indicate the need of appropriate tests, and patients are not informed that the drug-nitrite interaction and the consequent risk can be reduced to a large extent by consuming the nitrosatable drug with ascorbic acid.
Department of Internal Medicine, Division of Clinical Pharmacology and Toxicology, University of Genoa, Viale Benedetto XV, 2, I-16132 Genoa, Italy. Antonietta.Martelli@unige.it
Antonietta
A
Martelli
Giovanni
G
Brambilla
D000588:Amines / Q000737:chemistry / Q000633:toxicity*; D002273:Carcinogens / Q000737:chemistry / Q000633:toxicity*; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D009569:Nitric Oxide / Q000737:chemistry*
D000588:Amines; D002273:Carcinogens; D009153:Mutagens; D009569:Nitric Oxide