Hantson P, de Saint-Georges L, Mahieu P, Léonard E D, Crutzen-Fayt M C, Léonard A
Department of Intensive Care, Cliniques Universitaires St-Luc, Brussels, Belgium.
Mutat Res. 1996 Jul 5;368(3-4):293-300. doi: 10.1016/s0165-1218(96)90071-3.
The ability of paracetamol to induce structural chromosome aberrations in human peripheral blood lymphocytes in vivo was evaluated in volunteers who had been administered a single oral dose of 3 g paracetamol, in patients who had received 2 g of propacetamol by intravenous infusion every 6 h for at least 7 days, and in self-poisoned patients who, for suicidal reasons, had ingested more than 15 g paracetamol. In addition to the in vivo observations, the effectiveness of paracetamol to interfere with fusorial microtubule polymerisation was assayed in vitro in order to detect a possible effect of paracetamol on the distribution of chromosomes during cell division. The negative results obtained in all those assays strongly suggest that paracetamol has no mutagenic properties in human. There was, indeed, no significant difference in the percentage of abnormal cells before and after application of paracetamol in volunteers (0.2% before ingestion of 3 g paracetamol, 0.12% after 24 h, 0.04% after 72 h and 0.04% after 168 h) and in patients (0.5% of abnormal cells before treatment versus 0.44% after intravenous infusion of a total of 28 g paracetamol). Moreover, the yield of abnormal cells was not modified in self-poisoned persons (0.24%), in spite of an important decrease in the mitotic index of the PHA stimulated lymphocytes. In the in vitro assay, no inhibition of microtubule polymerisation was detected with concentrations of 2.5, 5 and 10 mM paracetamol.
在志愿者、接受丙帕他莫治疗的患者以及过量服用对乙酰氨基酚的自我中毒患者中，评估了对乙酰氨基酚在体内诱导人外周血淋巴细胞结构染色体畸变的能力。志愿者单次口服3 g对乙酰氨基酚，患者每6小时静脉输注2 g丙帕他莫，至少持续7天，自我中毒患者因自杀原因摄入超过15 g对乙酰氨基酚。除了体内观察外，还在体外检测了对乙酰氨基酚干扰纺锤体微管聚合的有效性，以检测对乙酰氨基酚在细胞分裂过程中对染色体分布的可能影响。所有这些试验得到的阴性结果强烈表明，对乙酰氨基酚对人类没有致突变特性。事实上，在志愿者中（服用3 g对乙酰氨基酚前异常细胞百分比为0.
