Dosimetry of ethylene oxide in the rat by quantitation of alkylated histidine in hemoglobin.
Dosimetry of ethylene oxide in the rat by quantitation of alkylated histidine in hemoglobin.
复制标题
通过定量血红蛋白中的烷基化组氨酸来测定大鼠中环氧乙烷的剂量。
DOI：
--
复制
发表时间：
1983
期刊：
影响因子：
--
通讯作者：
L. Ehrenberg
中科院分区：
文献类型：
--
作者：
S. Osterman;P. Farmer;D. Segerbäck;E. Bailey;C. Calleman;K. Svensson;L. Ehrenberg
从暴露于受控空气浓度环氧乙烷（0、10、33和100 ppm）的雄性Fischer 344大鼠中采集血样，6 h/天，5天/周，持续2年。从血红蛋白水解物中分离出N-（2-羟乙基）组氨酸，并通过气相色谱-质谱和氨基酸分析进行定量分析。在三种空气水平的环氧乙烷下，两组未暴露大鼠的烷基化程度分别为1.3和2.8 nmol羟乙基组氨酸/克血红蛋白，14、34和82 nmol/克血红蛋白。通过IP注射给予相同品种的大鼠两种浓度的放射性标记环氧乙烷。血红蛋白中的氨基酸和DNA中的鸟嘌呤-N-7从肝脏和睾丸的烷基化程度进行了测定。肝脏和睾丸DNA的烷基化程度分别约为血红蛋白烷基化程度预期值的150%和50%，该预期基于特定亲核位点的反应性与在这些位点获得的烷基化程度之间的直接比例，假设研究的不同组织中环氧乙烷的剂量相同。因此，根据血红蛋白烷基化数据确定的环氧乙烷体内剂量给出了DNA剂量的合理近似值。数据与环氧乙烷从组织中快速消除一致，生物半衰期估计为约10分钟。
Blood samples were obtained from male Fischer 344 rats exposed to controlled air concentrations of ethylene oxide; 0, 10, 33, and 100 ppm, 6 h/day, 5 days/week, for 2 years. N tau-(2-hydroxyethyl)histidine was isolated from hemoglobin hydrolysates and analyzed quantitatively by means of gas chromatography--mass fragmentography and by amino acid analysis. The degrees of alkylation found were 1.3 and 2.8 nmol hydroxyethylhistidine per gram hemoglobin in two groups of unexposed rats, and 14, 34, and 82 nmol per gram hemoglobin, respectively, at the three air levels of ethylene oxide. Rats of the same breed were given two concentrations of radiolabeled ethylene oxide by IP injection. The degrees of alkylation of amino acids in hemoglobin and of guanine-N-7 in DNA from livers and testes were determined. The degrees of alkylation of liver and testicular DNA were about 150% and 50%, respectively, of the values expected from the degree of alkylation of hemoglobin, basing the expectancy on a direct proportionality between the reactivity of the specific nucleophilic sites and the degree of alkylation obtained at these sites, assuming that the dose of ethylene oxide was the same in the different tissues studied. The in vivo dose of ethylene oxide determined from data on hemoglobin alkylation thus gives a reasonable approximation of the DNA dose. The data were in agreement with a fast elimination of ethylene oxide from the tissues, the biological half-life being estimated as about 10 min.