Neumann H G
Arch Toxicol. 1984 Nov;56(1):1-6. doi: 10.1007/BF00316343.
Genotoxic xenobiotics bind covalently to hemoglobin in vivo. The major reaction product of aromatic amines is a sulfinic acid amide resulting from the reaction of arylnitroso derivatives with SH-groups. Alkylating compounds react with cysteine, histidine and the terminal valine. The adducts are formed proportional to dose down to extremely small doses, they are stable throughout the life-span of the erythrocytes and accumulate upon repeated exposure. Methods for their determination in blood samples from experimental animals and humans are becoming available. Moreover, it has been demonstrated that for a given agent, a constant ratio exists between the reaction with tissue DNA and hemoglobin over a wide range of doses, which indicates that the reactions follow apparent first order kinetics. The extent of hemoglobin binding is therefore considered to be a relative measure of tissue dose, and should correlate much better with risk than exposure levels calculated from concentrations in the environment. Not only can the actual uptake be monitored more reliably, but also the individual's capacity to metabolically activate the absorbed agent. Biomonitoring of hemoglobin-bound metabolites represents a novel approach to control exposure to potential carcinogens, to correlate environmental exposure with tissue dose and eventually also with human risk.
具有基因毒性的外源性物质在体内与血红蛋白共价结合。芳香胺的主要反应产物是芳基亚硝基衍生物与巯基反应生成的亚磺酸酰胺。烷基化化合物与半胱氨酸、组氨酸和末端缬氨酸发生反应。加合物的形成与剂量成正比，直至极小剂量，它们在红细胞的整个生命周期内都很稳定，并在反复接触后积累。测定实验动物和人类血液样本中加合物的方法已逐渐可用。此外，已经证明，对于给定的一种物质，在很宽的剂量范围内，其与组织DNA和血红蛋白的反应之间存在恒定的比例关系，这表明这些反应遵循明显的一级动力学。因此，血红蛋白结合程度被认为是组织剂量的相对指标，与风险的相关性应该比根据环境浓度计算的暴露水平更好。不仅可以更可靠地监测实际摄入量，还能监测个体代谢激活吸收物质的能力。对血红蛋白结合代谢物进行生物监测代表了一种新方法，用于控制对潜在致癌物的暴露，将环境暴露与组织剂量相关联，并最终也与人类风险相关联。
