Browse

Biomarkers of exposure and effect as indicators of potential carcinogenic risk arising from in vivo metabolism of ethylene to ethylene oxide

Cited 52 time in Web of Science Cited 55 time in Scopus
Authors
Walker, Vernon E.; Wu, Kuen-Yuh; Upton, Patricia B.; Ranasinghe, Asoka; Scheller, Nova; Cho, Myung-Haeng.; Vergnes, Jane S.; Skopek, Thomas R.; Swenberg, James A.
Issue Date
2000-09
Citation
Carcinogenesis, Vol.21 No.9, pp.1661-1669
Abstract
The purposes of the present study were: (i) to investigate the potential use of several biomarkers as quantitative indicators of the in vivo conversion of ethylene (ET) to ethylene oxide (EO); (ii) to produce molecular dosimetry data that might improve assessment of human risk from exogenous ET exposures. Groups (n = 7/group) of male F344 rats and B6C3F1 mice were exposed by inhalation to 0 and 3000 p.p.m. ET for 1, 2 or 4 weeks (6 h/day, 5 days/ week) or to 0, 40, 1000 and 3000 p.p.m. ET for 4 weeks. N-(2-hydroxyethyl)valine (HEV), N7-(2-hydroxyethyl) guanine (N7-HEG) and Hprt mutant frequencies were assessed as potential biomarkers for determining the molecular dose of EO resulting from exogenous ET exposures of rats and mice, compared with background biomarker values. N7-HEG was quantified by gas chromatography coupled with high resolution mass spectrometry (GC-HRMS), HEV was determined by Edman degradation and GC-HRMS and Hprt mutant frequencies were measured by the T cell cloning assay. N7-HEG accumulated in DNA with repeated exposure of rodents to 3000 p.p.m. ET, reaching steady-state concentrations around 1 week of exposure in most tissues evaluated (brain, liver, lung and spleen). The dose-response curves for N7-HEG and HEV were supralinear in exposed rats and mice, indicating that metabolic activation of ET was saturated at exposures ≥1000 p.p.m. ET. Exposures of mice and rats to 200 p.p.m. EO for 4 weeks (as positive treatment controls) led to significant increases in Hprt mutant frequencies over background in splenic T cells from exposed rats and mice, however, no significant mutagenic response was observed in the Hprt gene of ET-exposed animals. Comparisons between the biomarker data for both unexposed and ET-exposed animals, the dose-response curves for the same biomarkers in EO-exposed rats and mice and the results of the rodent carcinogenicity studies of ET and EO suggest that too little EO arises from exogenous ET exposure to produce a significant mutagenic response or a carcinogenic response under standard bioassay conditions.
ISSN
0143-3334
URI
https://hdl.handle.net/10371/172358
DOI
https://doi.org/10.1093/carcin/21.9.1661
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse