Genotoxic and carcinogenic effects of gastrointestinal drugs.
This review provides a compendium of retrievable results of genotoxicity and carcinogenicity assays performed on marketed gastrointestinal drugs. Of the 71 drugs considered, 38 (53.5%) do not have retrievable data, whereas the other 33 (46.5%) have at least one genotoxicity or carcinogenicity test result. Of these 33 drugs, 15 tested positive in at least one genotoxicity assay and 13 in at least one carcinogenicity assay; 8 of them gave a positive response in both at least one genotoxicity assay and at least one carcinogenicity assay. Concerning the predictivity of genetic toxicology findings for the result(s) of long-term carcinogenesis assays, of 21 drugs with both genotoxicity and carcinogenicity data: 6 (28.6%) are neither genotoxic nor carcinogenic, 2 (9.5%) tested positive in at least one genotoxicity assay but were non-carcinogenic, 5 (23.8%) tested negative in genotoxicity assays but were carcinogenic and 8 (38.1%) gave a positive response in at least one genotoxicity assay and in at least one carcinogenicity assay. Only 12 (16.9%) of the 71 drugs examined have all data required by present guidelines for testing of pharmaceuticals, but a large fraction of them were developed and marketed prior the present regulatory climate.
Brambilla
Giovanni
G
Department of Internal Medicine, Division of Clinical Pharmacology and Toxicology, University of Genoa, Genoa, Italy.
Mattioli
Francesca
F
Martelli
Antonietta
A
D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D003257:Consumer Product Safety; D005765:Gastrointestinal Agents / Q000633:toxicity*; D006801:Humans; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009369:Neoplasms / Q000139:chemically induced; D018570:Risk Assessment
D002273:Carcinogens; D005765:Gastrointestinal Agents; D009153:Mutagens