Pereira M A, Chang L W
Chem Biol Interact. 1982 Mar 1;39(1):89-99. doi: 10.1016/0009-2797(82)90008-4.
The covalent binding of chemical carcinogens and mutagens to hemoglobin has been proposed as a dose monitor for environmental exposure. The binding of chloroform to hemoglobin in rats was demonstrated to result from the formation of addition adducts to amino acids in the globin. The altered amino acids were isolated with an amino acid analyzer employing ion exchange chromatography. The covalent binding of orally-administered [14C]chloroform to rat hemoglobin reached a peak within 10 h. Afterwards, the amount of chloroform bound decreased slowly with half remaining at 7 weeks. The extent of chloroform binding was linearly dependent upon dose between 0.1 and 100 mumol/kg. Above 100 mumol/kg chloroform the binding to hemoglobin increased at a reduced rate. The extent of [14C]chloroform binding resulting from either 10 daily doses of 0.1 mumol/kg or a single 1.0 mumol/kg was similar. The binding to hemoglobin in three strains of mice and rats varied from 85 +/- 7 mumol/g Hb for Swiss (CFN) mice to 152 +/- 14 for Fisher-344 rats. We have demonstrated that the binding of chloroform to hemoglobin appears to have the following attributes of a dose monitor: (1) easily accessible from laboratory animals (and humans); (2) dose dependent; (3) stability, so that exposure can be determined weeks after it has ceased; (4) integration of low exposures which individually would be undetectable.
化学致癌物和诱变剂与血红蛋白的共价结合已被提议作为环境暴露的剂量监测指标。已证明氯仿与大鼠血红蛋白的结合是由于其与珠蛋白中的氨基酸形成加成加合物所致。使用离子交换色谱的氨基酸分析仪分离出了发生改变的氨基酸。口服给予的[14C]氯仿与大鼠血红蛋白的共价结合在10小时内达到峰值。之后，结合的氯仿量缓慢下降，7周时仍有一半残留。氯仿的结合程度在0.1至100μmol/kg之间与剂量呈线性相关。氯仿剂量高于100μmol/kg时，其与血红蛋白的结合增加速率降低。10次每日剂量0.1μmol/kg或单次剂量1.0μmol/kg的[14C]氯仿所导致的结合程度相似。氯仿与三种品系小鼠和大鼠血红蛋白的结合量从瑞士（CFN）小鼠的85±7μmol/g Hb到费希尔-344大鼠的152±14μmol/g Hb不等。我们已经证明，氯仿与血红蛋白的结合似乎具有剂量监测指标的以下特性：（1）易于从实验动物（和人类）获取；（2）剂量依赖性；（3）稳定性，因此在暴露停止数周后仍可确定暴露情况；（4）整合低水平暴露，而这些低水平暴露单独来看是无法检测到的。
