采用中国仓鼠肺成纤维细胞系的体外微核试验评估 N-亚硝基酮咯烷和氯胺酮的遗传毒性效应。
Genotoxic effects of N-nitrosoketamine and ketamine as assessed by in vitro micronucleus test in Chinese hamster lung fibroblast cell line.
机构信息
Department of Public Health and Environmental Medicine, The Jikei University School of Medicine, 3-25-8, Nishishinbashi, Minato-ku, 105-8461, Tokyo, Japan,
出版信息
Environ Health Prev Med. 2006 May;11(3):120-7. doi: 10.1265/ehpm.11.120.
OBJECTIVES
Ketamine hydrochloride (KT) is a secondary amine that has been safely used as an injectable anesthetic and analgesic to avoid the production of nitroso compounds in the stomach. However, ketamine in the tablet form has recently become an abused, recreational drug. The aim of this study was to investigate the genotoxic effects of N-nitrosoketamine (NKT) and KT on the basis of an in vitro micronucleus (MN) test using a Chinese hamster lung fibroblast cell line (CHL/IU).
METHODS
NKT was synthesized from KT in our laboratory. In the MN tests, CHL/IU cells were continuously treated with either NKT or KT for 24, 48, or 72 hours without the S9 mix. The cells were also treated with NKT or KT with or without the S9 mix for 6 hours, followed by a recovery period of 18, 42, or 66 hours (short-term treatment). The results were considered to be statistically significant when the p-values of both Fisher's exact test and the trend test were less than 0.05.
RESULTS
After the short-term treatment with either NKT or KT with and without the S9 mix, the frequency of micronuclei significantly increased. However, the frequency of micronuclei did not significantly increase after the continuous treatment with either NKT or KT. Both NKT and KT were determined to be genotoxic in the short-term treatment with or without the S9 mix, but they were determined to be nongenotoxic in continuous treatment.
CONCLUSION
Our findings suggest that NKT has a stronger genotoxic effect than KT.
目的
盐酸氯胺酮（KT）是一种仲胺，已被安全用作注射用麻醉剂和镇痛药，以避免在胃中产生亚硝基化合物。然而，最近片剂形式的氯胺酮已成为一种被滥用的娱乐性药物。本研究旨在基于中国仓鼠肺成纤维细胞系（CHL/IU）的体外微核（MN）试验，研究 N-亚硝基氯胺酮（NKT）和 KT 的遗传毒性作用。
方法
NKT 是由我们实验室从 KT 合成的。在 MN 试验中，CHL/IU 细胞连续 24、48 或 72 小时不添加 S9 混合物，用 NKT 或 KT 处理。细胞也用 NKT 或 KT 与或不与 S9 混合物处理 6 小时，然后进行 18、42 或 66 小时的恢复期（短期处理）。当 Fisher 确切检验和趋势检验的 p 值均小于 0.05 时，结果被认为具有统计学意义。
结果
无论是短期处理还是短期处理与 S9 混合物一起处理 NKT 或 KT，微核的频率都显著增加。然而，连续用 NKT 或 KT 处理时，微核的频率并没有显著增加。无论是否有 S9 混合物，NKT 和 KT 都被确定为短期处理的遗传毒性物质，但在连续处理时被确定为非遗传毒性物质。
结论
我们的研究结果表明，NKT 比 KT 具有更强的遗传毒性作用。
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