Fahmy M A, Aly F A
Department of Genetics and Cytology, National Research Centre, Dokki, Cairo, Egypt.
J Appl Toxicol. 2000 May-Jun;20(3):231-8. doi: 10.1002/(sici)1099-1263(200005/06)20:3<231::aid-jat653>3.0.co;2-t.
The genotoxic effect of cadmium chloride was evaluated in chromosomes of experimental mice using in vivo and in vitro studies. In vivo the induction of micronuclei, sister chromatid exchange in mouse bone marrow and chromosomal aberrations in both somatic and germ cells was investigated. Doses 1.9, 5.7 and 7.6 mg kg(-1) body wt. (single i.p. treatment) induced a significant and dose-dependent increase in the percentage of polychromatic erythrocytes with micronuclei. Such a percentage reached 2.1% with the highest tested dose, compared with 0.57% for the control (non-treated) and 2.2% for mitomycin c as the positive control. The dose of 1.9 mg kg(-1) body wt. had no significant effect with respect to sister chromatid exchange (SCE) but the doses of 5.7 and 7.6 mg kg(-1)body wt. increased the frequency of SCEs significantly. The frequency of SCE reached 7.35 +/- 0.26 per cell after treatment with the highest tested dose, which is a less than twofold increase compared with the control frequency of 4.6 +/- 0.42 per cell. However mitomycin c induced a much higher effect (12.1 +/- 0.73). Cadmium chloride also induced a significant increase in the percentage of chromosomal aberrations in mouse bone marrow at the doses of 5.7 and 9.5 mg kg(-1) body wt. (single i.p. treatment). The effect is a function of cadmium chloride concentration. Moreover, cadmium chloride induced its maximum effect concerning the induction of chromosomal aberrations in mouse bone marrow cells 24 h after treatment, compared with 12 and 48 h. In germ cells, chromosomal aberrations were observed in mouse spermatocytes 12 days post-treatment with the dose of 5.7 mg kg(-1) body wt. Moreover, a pronounced reduction in the number of spermatocytes was observed after administration of cadmium chloride (0.9, 1.9 and 5.7 mg kg(-1) body wt.) In in vitro studies, the three tested concentrations of 10, 15 and 20 microgram ml(-1) cadmium chloride induced a statistically significant increase in the frequency of SCEs in cultured mouse spleen cells. The concentrations of 15 and 20 microgram ml(-1) also induced chromosomal aberrations in mouse spleen culture. The ability of vitamin C (l-ascorbic acid) to minimize the incidence of chromosomal aberrations induced by cadmium chloride in cultured mouse spleen cells was investigated. Vitamin C at the concentrations of 3 and 6 microgram ml(-1) significantly minimized the percentage of aberrant cells induced by cadmium chloride.
通过体内和体外研究，评估了氯化镉对实验小鼠染色体的遗传毒性作用。在体内，研究了小鼠骨髓中微核的诱导、姐妹染色单体交换以及体细胞和生殖细胞中的染色体畸变。剂量为1.9、5.7和7.6mg/kg体重（单次腹腔注射）可诱导含微核的多染性红细胞百分比显著且呈剂量依赖性增加。在最高测试剂量下，该百分比达到2.1%，而对照组（未处理）为0.57%，丝裂霉素C作为阳性对照为2.2%。1.9mg/kg体重的剂量对姐妹染色单体交换（SCE）没有显著影响，但5.7和7.6mg/kg体重的剂量显著增加了SCE的频率。在最高测试剂量处理后，SCE频率达到每细胞7.35±0.26，与每细胞4.6±0.42的对照频率相比增加不到两倍。然而，丝裂霉素C诱导的效应更高（12.1±0.73）。氯化镉在5.7和9.5mg/kg体重的剂量下（单次腹腔注射）也可诱导小鼠骨髓中染色体畸变百分比显著增加。该效应是氯化镉浓度的函数。此外，与12小时和48小时相比，氯化镉在处理后24小时对小鼠骨髓细胞染色体畸变诱导的影响最大。在生殖细胞中，在以5.7mg/kg体重的剂量处理12天后，在小鼠精母细胞中观察到染色体畸变。此外，在给予氯化镉（0.9、1.9和5.7mg/kg体重）后，观察到精母细胞数量明显减少。在体外研究中，测试的10、15和20μg/ml三种氯化镉浓度可诱导培养的小鼠脾细胞中SCE频率有统计学意义的增加。15和20μg/ml的浓度也可诱导小鼠脾培养物中的染色体畸变。研究了维生素C（L-抗坏血酸）使氯化镉在培养的小鼠脾细胞中诱导的染色体畸变发生率最小化的能力。3和6μg/ml浓度的维生素C可显著降低氯化镉诱导的异常细胞百分比。
