Lack of DNA fragmentation in rats treated with high oral doses of drugs acting on the central nervous system.

: Five drugs acting on the central nervous system-chlorpromazine, triflupromazine, thioridazine, chlordiazepoxide, and ethosuximide--which provided conflicting results in previous genotoxicity assays have been tested for their DNA-damaging activity in vivo. The capability of these drugs of inducing DNA fragmentation was investigated by the use of two different techniques: rate of DNA strand separation in alkali as measured by hydroxylapatite chromatography, and changes of DNA viscometric behavior as detected by a new highly sensitive method. DNA damage, as checked by the first technique, was absent in both liver and gastric mucosa of rats given a single p.o. administration of 1/2 LD50 of the drugs. These negative results were confirmed by the subsequent viscometric analysis of liver DNA from rats treated with the same doses.