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.
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002491:Central Nervous System Agents / Q000494:pharmacology* / Q000633:toxicity; D004247:DNA / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology; D007928:Lethal Dose 50; D008297:Male; D009691:Nucleic Acid Denaturation; D051381:Rats; D011919:Rats, Inbred Strains; D014783:Viscosity
D002491:Central Nervous System Agents; D004247:DNA