Jenderny J, Walk R A, Hackenberg U, Röhrborn G
Institut für Humangenetik und Anthropologie der Universität Düsseldorf, F.R.G.
Mutat Res. 1988 Feb;203(1):1-10. doi: 10.1016/0165-1161(88)90002-7.
The genotoxic effects of cyclophosphamide (CPP), a human and animal carcinogen requiring metabolic activation, were studied in bone marrow cells of mice and Chinese hamsters, analyzing chromosome abnormalities (CA) and sister-chromatid exchange (SCE) after a 2-h inhalation or a single intraperitoneal administration. In order to compare the genotoxicity after the different routes of administration in the dose range of 10-110 mg CPP/kg body weight, the systemic dose obtained by inhalation was calculated from blood concentrations and the inhalation duration after an analysis of the CPP blood kinetics. In NMRI mice the frequency of bone marrow cells with chromosome abnormalities was higher after aerosol exposure than after intraperitoneal administration of comparable CPP doses. In Chinese hamsters the CA frequency was similar with both exposure routes. Inhaled CPP was found to induce a higher frequency of CA and SCE in the bone marrow cells of mice compared to those of Chinese hamsters. The findings suggest that for genotoxins requiring metabolic activation species differences exist with respect to the influence of the route of entry and the sensitivity of bone marrow cells.
环磷酰胺（CPP）是一种需要代谢激活的人类和动物致癌物，本研究通过2小时吸入或单次腹腔注射，分析小鼠和中国仓鼠骨髓细胞中的染色体异常（CA）和姐妹染色单体交换（SCE），研究其遗传毒性作用。为了比较10-110mg CPP/kg体重剂量范围内不同给药途径后的遗传毒性，在分析CPP血液动力学后，根据血液浓度和吸入持续时间计算吸入获得的全身剂量。在NMRI小鼠中，气溶胶暴露后骨髓细胞中染色体异常的频率高于腹腔注射相当剂量的CPP后。在中国仓鼠中，两种暴露途径的CA频率相似。与中国仓鼠相比，吸入的CPP在小鼠骨髓细胞中诱导更高频率的CA和SCE。研究结果表明，对于需要代谢激活的遗传毒素，在进入途径的影响和骨髓细胞的敏感性方面存在物种差异。
