In vivo and in vitro ethylene oxide exposure of human lymphocytes assessed by chemical stimulation of unscheduled DNA synthesis.

Abstract

Factory workers exposed to ethylene oxide (EO), 0.5-1.0 ppm in factory air, together with matched controls from the same factory, were examined for evidence of toxic exposure by measurement of unscheduled DNA synthesis (UDS) induced by N-acetoxy-2-acetylaminofluorene (NA-AAF) and of chromosome aberrations in peripheral lymphocytes. The total chromatid gaps plus breaks were significantly elevated and NA-AAF-induced UDS was significantly reduced in the EO-exposed group as compared with the unexposed control group. The NA-AAF-induced UDS values negatively correlated to the duration (yr) of EO exposure (r = -0.45, p less than 0.02) and the number of chromosome breaks (r = -0.61, p less than 0.05), indicating an inhibition in vivo of DNA-repair capacity by EO. These data were verified in vitro by biochemical and autoradiographic studies of EO-induced UDS in human blood cells. Above 2 mM EO, UDS was inhibited in lymphocytes whether they were cultured for 24 or 122 h after alkylation with EO. Even at the subtoxic EO dose of 0.1 mM, lymphocytes were sensitized to additional exposures of NA-AAF, so that cytotoxicity was increased to 40% compared with 5% for the controls even though UDS was unaffected. It is concluded that EO was toxic to lymphocytes, even when they were sensitized at non-toxic EO doses to the cytotoxic action of other mutagens (e.g. NA-AAF), and the cells that did survive above 2 mM EO were inhibited in their DNA-repair capacity as judged by reduced UDS.

• Authors: R W Pero, B Widegren, B Högstedt, F Mitelman
• Journal: Mutation research (Mutat Res) Vol. 83 Issue 2 Pg. 271-89 (Sep 1981) ISSN: 0027-5107 [Print] Netherlands
• PMID: 7300850 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA
• Ethylene Oxide

Topics

• Adult
• Chromosomes, Human (ultrastructure)
• DNA (biosynthesis)
• DNA Repair (drug effects)
• Environmental Exposure
• Ethylene Oxide (pharmacology)
• Female
• Humans
• Karyotyping
• Lymphocytes (metabolism, ultrastructure)