Genotoxicity and carcinogenicity testing of pharmaceuticals: correlations between induction of DNA lesions and carcinogenic activity.
This survey is a compendium of the results of DNA lesions assays (DNA adducts, DNA strand breaks, DNA repair synthesis) and of the results of carcinogenicity assays of 146 pharmaceuticals. Of these drugs, 55 (37.7%) tested negative in both DNA lesions assay(s) and in carcinogenicity assay(s); 65 (44.5%) tested negative in DNA lesions assay(s), but gave a positive response in at least one carcinogenicity assay; 6 (4.1%) tested positive in at least one DNA lesions assay, but negative in carcinogenicity assay(s); 20 (13.7%) tested positive in at least one DNA lesions assay and in at least one carcinogenicity assay. Concerning the predictivity of DNA lesions assays findings for the results of long-term carcinogenesis assays performed in mice, rats or other species, concordance was found to exist for the 46.2% of pharmaceuticals in the case of DNA adducts, for 63.1% in the case of DNA strand breaks, and for 47.3% in the case of DNA repair synthesis (UDS).
Brambilla
Giovanni
G
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
Mattioli
Francesca
F
Robbiano
Luigi
L
Martelli
Antonietta
A
D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods*; D018736:DNA Adducts; D053960:DNA Breaks; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics*; D009152:Mutagenicity Tests / Q000379:methods*; D004364:Pharmaceutical Preparations
D018736:DNA Adducts; D004364:Pharmaceutical Preparations