Alkaline elution of DNA as a method for assessing genotoxic effects of drugs: its application to a series of antiviral compounds.
Various techniques are available for the evaluation of the genotoxic potential of drugs and chemicals, some of which utilize as targets mammalian cells grown in vitro. Among these techniques alkaline elution of DNA has the advantage of rapidity and low cost, and can be performed on easily grown leukemia cell lines. To test the applicability of the method to pharmaceutical compounds, we used DNA-alkaline elution with a series of antiviral agents with variable DNA-damaging activity. 5-Iodo-2'-deoxyuridine (5-IdU), 5-bromo-2'-deoxyuridine (5-BrdU) and 5-trifluoromethyl-2'-deoxyuridine (F3dT) increased the DNA elution rate over controls in a dose-dependent fashion, 9-beta-D-arabinofuranosyladenine (ARA-A) had a marginal effect. 9-(2-Hydroxyethoxymethyl)guanine(acyclovir,ACV) and 5-(2-bromovinyl)-2-deoxyuridine (5-BrVdU), selective antiviral compounds, did not vary alkaline elution profiles. These results fully support the use of alkaline elution of DNA as a standard procedure in the evaluation of the genotoxic effect of drugs.
D000818:Animals; D000998:Antiviral Agents / Q000633:toxicity*; D002460:Cell Line; D004247:DNA / Q000032:analysis*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D019286:Endopeptidase K; D010450:Endopeptidases; D051379:Mice; D009152:Mutagenicity Tests / Q000379:methods*
D000998:Antiviral Agents; D004247:DNA; D010450:Endopeptidases; D019286:Endopeptidase K