Director A E, Tucker J D, Ramsey M J, Nath J
Applied Cellular Radiobiology, Armed Forces Radiobiology Research Institute, Bethesda, Maryland,
Environ Mol Mutagen. 1998;32(2):139-47.
Environmental exposure to mutagens is believed to play a significant role in human carcinogenesis. Determination of the in vivo effects of a single mutagen is best done in laboratory animals because humans are exposed to a variety of mutagens both in their diet and in the rest of their environment. In this study, C57BL/6N female mice were used to analyze the effect on chromosomes of chronic ingestion of a mutagen dissolved in drinking water. Cyclophosphamide (CP) or urethane (ethyl carbamate, EC) were dissolved in sterile drinking water at concentrations of 0, 32, 64, and 96 ppm or 0, 5,000, 10,000, and 15,000 ppm, respectively. All exposures began at 8 weeks of age and continued through the 20th week unless terminated earlier due to toxicity. Body weights and water consumption were measured weekly. Blood and bone marrow were taken from approximately five mice per exposure group at 4, 8, and 12 weeks from the start of exposure. All mice remaining after 12 weeks received drinking water without any carcinogen for an additional 6 weeks to determine if induced aberrations persisted. Chromosome translocations, measured by painting, were not induced in blood or bone marrow cells at any time point for either chemical. However, both carcinogens induced significant increases in micronucleated normochromatic erythrocytes, indicating that the carcinogens reached the tissues examined in these experiments. These results indicate that chronic exposure of mice to chemical carcinogens induces chromosome breakage measurable by micronuclei. However, the breakage and reunion necessary to see chromosome exchanges such as translocations were not observed in this study.
环境中诱变剂的暴露被认为在人类致癌过程中起重要作用。由于人类在饮食及其他环境中会接触多种诱变剂，因此确定单一诱变剂的体内效应最好在实验动物中进行。在本研究中，使用C57BL/6N雌性小鼠来分析长期摄入溶解于饮用水中的诱变剂对染色体的影响。环磷酰胺（CP）或氨基甲酸乙酯（EC）分别以0、32、64和96 ppm或0、5000、10000和15000 ppm的浓度溶解于无菌饮用水中。所有暴露从8周龄开始，持续到第20周，除非因毒性提前终止。每周测量体重和饮水量。在暴露开始后的第4、8和12周，从每个暴露组中大约五只小鼠采集血液和骨髓。12周后剩余的所有小鼠再额外饮用6周不含任何致癌物的水，以确定诱导的畸变是否持续存在。通过染色体涂染测量的染色体易位在任何时间点的血液或骨髓细胞中均未被这两种化学物质诱导产生。然而，两种致癌物均诱导正常染色红细胞微核显著增加，表明致癌物到达了这些实验中所检测的组织。这些结果表明，小鼠长期接触化学致癌物会诱导可通过微核测量的染色体断裂。然而，在本研究中未观察到染色体交换（如易位）所需的断裂和重接。
