Wilmer J L, Erexson G L, Kligerman A D
Basic Life Sci. 1984;29 Pt B:561-7. doi: 10.1007/978-1-4684-4892-4_5.
Erythrocytes [red blood cells (RBCs)] possess aniline hydroxylase activity. When aniline interacts with ferrohemoglobin in the presence of molecular oxygen, oxidation of nitrogen and ring carbons occurs. Thus, apart from the liver, RBCs may represent an important site of aniline metabolism. Because 2 metabolites of aniline, o-aminophenol and phenylhydroxylamine, can induce sister chromatid exchanges (SCEs), we examined the ability of RBCs and hemoglobin to activate aniline to genotoxic intermediates as evidenced by SCE induction in human lymphocytes. Aniline HCI (0.05-1.0 mM) induced significant concentration-related increases in the SCE frequency only in the whole blood cultures. Similarly, inhibition of cell cycle kinetics by aniline was observed only in the whole blood cultures, as shown by a concentration-dependent decrease in the percentage of third- (and later) division metaphases. Mitotic indices were not affected significantly at any concentration of aniline or hemoglobin. Hemoglobin (500 or 1,000 micrograms/ml) alone induced significant concentration-related increases in SCEs in the mononuclear leukocyte cultures. Therefore, human mononuclear leukocytes do not activate aniline to genotoxic intermediates capable of inducing SCEs during a 48-hr exposure. However, the inclusion of RBCs and granulocytes provides an activation system as demonstrated by a small, but statistically significant increase in the SCE frequency in the whole blood cultures. The weak genotoxicity of hemoglobin may be related to production of oxygen radicals during autoxidation to methemoglobin.(ABSTRACT TRUNCATED AT 250 WORDS)
红细胞[红细胞（RBCs）]具有苯胺羟化酶活性。当苯胺在分子氧存在的情况下与高铁血红蛋白相互作用时，氮和环碳会发生氧化。因此，除肝脏外，红细胞可能是苯胺代谢的一个重要部位。由于苯胺的两种代谢产物邻氨基苯酚和苯胲可诱导姐妹染色单体交换（SCEs），我们检测了红细胞和血红蛋白将苯胺激活为遗传毒性中间体的能力，这可通过人淋巴细胞中SCE诱导来证明。仅在全血培养物中，盐酸苯胺（0.05 - 1.0 mM）可诱导SCE频率出现显著的浓度相关增加。同样，仅在全血培养物中观察到苯胺对细胞周期动力学的抑制，表现为第三（及更晚）分裂中期百分比的浓度依赖性降低。在任何苯胺或血红蛋白浓度下，有丝分裂指数均未受到显著影响。单独的血红蛋白（500或1000微克/毫升）可诱导单核白细胞培养物中SCE出现显著的浓度相关增加。因此，人单核白细胞在48小时暴露期间不会将苯胺激活为能够诱导SCE的遗传毒性中间体。然而，红细胞和粒细胞的存在提供了一个激活系统，全血培养物中SCE频率虽有小幅但具有统计学意义的增加就证明了这一点。血红蛋白的弱遗传毒性可能与自身氧化为高铁血红蛋白过程中氧自由基的产生有关。（摘要截断于250字）
