Inhibition of sulfotransferase affecting unscheduled DNA synthesis induced by 2-acetylaminofluorene: an in vivo and in vitro comparison.
The unscheduled DNA repair (UDS) assay was conducted using the in vivo and in vitro procedures to investigate the role of arylsulfotransferases (AST) in the genotoxicity of 2-acetylaminofluorene (AAF). The in vivo assay had 4 groups of rats that consisted of those treated with pentachlorophenol (PCP), PCP and AAF, or AAF and an untreated control. The in vitro assay used hepatocytes from 3-methylcholanthrene or corn oil (control) treated rats. In both the in vivo and in vitro UDS assays AAF induced DNA damage. PCP, an inhibitor of arylsulfotransferase, significantly decreased AAF induced DNA damage. In the in vivo assay, PCP induced a significant increase in UDS and confounded an investigation of the role of sulfotransferase. The in vitro UDS assay more clearly defined the effect of PCP on AAF genotoxicity.
Monteith
D K
DK
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, MI 48105.
D015073:2-Acetylaminofluorene / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D015239:Arylsulfotransferase / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009153:Mutagens; D051381:Rats; D011919:Rats, Inbred Strains
D009153:Mutagens; D015073:2-Acetylaminofluorene; D015239:Arylsulfotransferase