Madrigal-Bujaidar E, Velazquez-Guadarrama N, Morales-Ramirez P, Mendiola M T
Laboratorio de Genética. Escuela Nacional de Ciencias Biológicas, I.P.N., Carpio y Plan de Ayala, México.
Teratog Carcinog Mutagen. 2002;22(2):83-91. doi: 10.1002/tcm.10003.
The initial purpose of the study was to determine the potential of acetaldehyde (Ace) to increase the rate of sister-chromatid exchanges (SCEs) in mouse spermatogonia. We tested four doses of Ace (from 0.4 to 400.0 mg/kg), including a negative and a positive control group (distilled water and cyclophosphamide, respectively). The results showed that all tested doses were SCE inducers. The highest tested dose increased the control level more than three times. Also, the cumulative frequencies of SCEs per cell were higher in the Ace-treated animals than in the control cells. Ace is transformed into acetate through the enzyme aldehyde dehydrogenase, a process that may be blocked by disulfiram (Dis) generating the accumulation of Ace. The second purpose of the study was to determine if the administration of Dis (150 mg/kg) could increase the SCE rate produced by non-genotoxic doses of Ace. (0.004 and 0.04 mg/kg). The animals treated with the two doses of Ace alone showed no increase in the frequency of SCEs; also, Dis by itself was not an SCE inducer. However, the groups of animals previously treated with Dis showed an increase of 31 and 60% with respect to the values obtained with the two doses of Ace alone. Furthermore, the cumulative frequencies of SCEs per cell were higher in the animals administered with both compounds together than in those treated with them separately. These results suggest the need to extend this type of study to other models.
该研究的最初目的是确定乙醛(Ace)增加小鼠精原细胞中姐妹染色单体交换(SCE)率的潜力。我们测试了四种剂量的Ace(0.4至400.0毫克/千克),包括一个阴性对照组和一个阳性对照组(分别为蒸馏水和环磷酰胺)。结果表明,所有测试剂量都是SCE诱导剂。测试的最高剂量使对照水平增加了三倍多。此外,Ace处理组动物每个细胞的SCE累积频率高于对照细胞。Ace通过醛脱氢酶转化为乙酸盐,双硫仑(Dis)可能会阻断这一过程,从而导致Ace积累。该研究的第二个目的是确定给予Dis(150毫克/千克)是否会增加非遗传毒性剂量的Ace(0.004和0.04毫克/千克)所产生的SCE率。单独用两种剂量的Ace处理的动物,其SCE频率没有增加;此外,Dis本身不是SCE诱导剂。然而,先前用Dis处理的动物组相对于单独用两种剂量的Ace所获得的值分别增加了31%和60%。此外,同时给予两种化合物的动物每个细胞的SCE累积频率高于分别用它们处理的动物。这些结果表明需要将这类研究扩展到其他模型。