에틸렌옥사이드에 폭로된 흰쥐의 혈액에 형성된 헤모글로빈 부가체에 대한 연구

A study on formation of hemoglobin adduct in blood of mice inhaled with ethylene oxide

Ethylene oxide is a genotoxic carcinogen with widespread uses as industrial chemical intermediate and gaseous sterilant. 2-hydroxyethylated N-terminal valine in Hb is a good biomarker for biological monitoring of ethylene oxide exposure, because of its stability. For measuring the hemoglobin adduct formed by exposure of ethylene oxide, we studied the determination of (N-2-hydroxy-ethyl)valine(HEV) in hemoglobin adduct by using GC/MS. Firstly we synthesized HEV with 2-amino-ethanol and bromoisovaleric acid(BIVA) and confirmed it with GC/MS-FID. Its fragmentations were m/z 116(base ion, M+.45) and m/z 130(M+.31). For measuring HEV with higher sensitivity, we use derivatives which were PFPITH(pentafluorophenylisothiocianate) and TBDMS(tributyldimethylsilylation) by using Edman procedure. Its fragmentation were m/z 425(M+.57), m/z 383(M+.99) and m/z 172(M+.310) by using GC/MS. We did biological monitoring for mice inhalation exposure with 400 ppm ethylene oxide. The concentrations of hemoglobin adduct were 1683.8 and 51204(nmol g-1 globin) at 0.5 hr/day 400 ppm ethylene oxide inhalation exposure group, and 63117 and 22659.4(nmol g-1 globin) at 1.0 hr/day 400 ppm ethylene oxide inhalation exposure for 1 and 4 weeks, respectively. We confirmed that (N-2-hydroxy-ethyl)valine(HEV) of hemoglobin was a good biomarker for biomonitoring of ethylene oxide exposure, and can measured with derivatives such as PFPITH(pentafluorophenylisothiocianate) and TBDMS(tributyldimethylsilylation) by using GC/MS.