Genotoxic effects of styrene-7,8-oxide in human white blood cells: comet assay in relation to the induction of sister-chromatid exchanges and micronuclei.
Styrene is used in the production of plastics, resins and rubber. The highest human exposures to styrene take place by inhalation during the production of fiberglass reinforced plastics. Styrene is metabolized mainly in the liver to styrene-7,8-oxide (SO), its principal in vivo mutagenic metabolite. In this study, human peripheral white blood cells were exposed to several SO concentrations (10-200 microM) in order to evaluate its genotoxic properties by means of comet assay, sister-chromatid exchanges (SCE) and cytokinesis-blocked micronucleus (MN) test, in addition to determine its clastogenic or aneugenic properties by combining MN with fluorescence in situ hybridization (FISH) procedures. Our results show that SO induces DNA damage, SCE and MN in human leukocytes in vitro at concentrations above 50 microM, and that there is a strong relationship between DNA damage, as measured by the comet assay, and cytogenetic damage induced by SO at the doses employed. SO shows preferentially a clastogenic activity and produces a cytostatic effect at high doses, reflected by the significant decrease of the calculated proliferation indices. A good dose-effect relationship is obtained in the three tests performed at the concentration range assayed.
Laffon
B
B
Dpto. Biología Celular y Molecular, Facultad de Ciencias, Universidade da Coruña, Campus da Zapateira s/n, 15071 A, Coruna, Spain.
Pásaro
E
E
Méndez
J
J
D000328:Adult; D020552:Comet Assay; D004852:Epoxy Compounds / Q000633:toxicity*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007962:Leukocytes / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D009153:Mutagens / Q000633:toxicity*; D012854:Sister Chromatid Exchange
D004852:Epoxy Compounds; D009153:Mutagens; C013690:styrene oxide