title: Unscheduled DNA synthesis in human hair follicles after in vitro exposure to 11 chemicals: comparison with unscheduled DNA synthesis in rat hepatocytes.
abstract: A new method is described to investigate unscheduled DNA synthesis (UDS) in human tissue after exposure in vitro: the human hair follicle. A histological technique was applied to assess cytotoxicity and UDS in the same hair follicle cells. UDS induction was examined for 11 chemicals and the results were compared with literature findings for UDS in rat hepatocytes. Most chemicals inducing UDS in rat hepatocytes raised DNA repair at comparable concentrations in the hair follicle. However, 1 of 9 chemicals that gave a positive response in the rat hepatocyte UDS test, 2-acetylaminofluorene, failed to induce DNA repair in the hair follicle. Metabolizing potential of hair follicle cells was shown in experiments with indirectly acting compounds, i.e., benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene and dimethylnitrosamine. The results support the conclusion that the test in its present state is valuable as a screening assay for the detection of unscheduled DNA synthesis. Moreover, the use of human tissues may result in a better extrapolation to man.
authors.affiliation: RCC NOTOX B.V., 's-Hertogenbosch, The Netherlands.
authors.forename: Y H
authors.initials: YH
authors.lastname: van Erp
authors.forename: M J
authors.initials: MJ
authors.lastname: Koopmans
authors.forename: P R
authors.initials: PR
authors.lastname: Heirbaut
authors.forename: J C
authors.initials: JC
authors.lastname: van der Hoeven
authors.forename: P J
authors.initials: PJ
authors.lastname: Weterings
mesh_terms: D000818:Animals; D001345:Autoradiography; D001711:Biotransformation; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D006197:Hair / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D013936:Thymidine / Q000378:metabolism
chemical_list: D009153:Mutagens; D004247:DNA; D013936:Thymidine