Sensitivity to cisplatin-induced mutations and elevated chromosomal aberrations in lymphocytes from sickle cell disease patients

Sickle cell disease (SCD) is an inherited disorder caused by a single nucleotide substitution in the β-globin gene. The clinical heterogeneity observed in SCD patients has been attributed to environmental and genetic factors. The patients are subjected to increased oxidative stress, particularly during vaso-occlusive crises and acute chest pain. Another possible cause of oxidative stress in SCD is the high concentration of iron in the patients’ plasma. The increase in oxidative stress could be a relevant risk factor for mutagenesis and carcinogenesis. Studies on the frequency of basal chromosomal aberrations in cultured lymphocytes from SCD patients have not been reported so far. In order to contribute to the understanding of the role of the different biomarkers and their relationship with the extremely variable clinical manifestation of SCD, we investigated the frequency of chromosome damage in peripheral lymphocytes from sickle cells patients and healthy controls. We found an increased frequency of chromosome damage and percentage of aberrant metaphases in these patients when compared with control subjects, even at basal values (p < 0.05). In the cytogenetic sensitivity assay, the results showed that these patients presented a marked decrease in the mitotic index values compared with healthy controls. Cisplatin-induced chromosomal damage in lymphocytes from these patients was significantly higher than the frequency measured in healthy controls. The results obtained in the present study showed that more investigations are needed in order to elucidate the susceptibility to genomic instability of SCD patients.     

Genotoxicity testing of Cecropia obtusifolia extracts in two in vivo assays: the wing somatic mutation and recombination test of Drosophila and the human cytokinesis-block micronucleus test

Cecropia obtusifolia Bertol. (Cecropiaceae) is a tree that grows in secondary vegetation in the tropical rain forest along both coasts of Mexico. Its leaves are used in folk medicine for the treatment of diabetes mellitus type 2. The aim of the present studies was the evaluation of possible genotoxic effects of the aqueous extract from the leaves of Cecropia obtusifolia by means of two different experimental assay models: the wing somatic mutation and recombination test in flies and the micronucleus test from lymphocytes obtained from patients treated with the extract. No toxicity was found to be induced by the leaves of Cecropia obtusifolia. The Drosophila wing somatic mutation and recombination test (SMART) was applied in the standard version with basal biotransformation activity as well as in a variant version with increased cytochrome P450-dependent bioactivation capacity. The ranges of exposure concentrations for these genotoxicity experiments were between 0.82 and 13.32 mg/ml. The extract did not produce any genotoxic effect; however it showed a non significant antigenotoxic effect. The human micronucleus assay in vivo was performed with cultured lymphocytes obtained from six diagnosed type 2 diabetic patients treated daily with 13.5 g of the aqueous extract between 32 and 85 days. No statistically significant increases in cytotoxicity and/or genotoxicity between control and diabetic blood samples were observed.     

马兜铃酸对小鼠淋巴瘤细胞的致突变性

目的 研究马兜铃酸的遗传毒性.方法 应用小鼠淋巴瘤细胞致突变试验检测马兜铃酸的遗传毒性.分别以15、30、60和120 μg/ml的马兜铃酸染毒小鼠淋巴瘤细胞L5178Y,在加和不加S9条件下观察细胞的突变频率.结果 在加和不加S9条件下,马兜铃酸染毒剂量≥30 μg/ml时,突变频率与对照相比较,差异均有统计学意义(P＜0.05),且有剂量依赖关系.结论 马兜铃酸对哺乳动物小鼠淋巴瘤细胞有一定的致突变性.     

生物可吸收性涂层补片的细胞毒性和遗传毒性研究

生物可吸收性涂层补片在应用于临床前必须进行一系列生物学评价以保证其安全性,细胞毒性和遗传毒性研究是其体外筛选部分。细胞毒性研究以补片浸提液接触受试细胞,观察细胞的毒性反应。生物可吸收性涂层补片浸提液1.5 cm2/ml时,细胞毒性反应1级;生物可吸收性涂层补片浸提液3 cm2/ml时,细胞毒性反应2级。遗传毒性研究包括两个试验,细菌回复突变试验结果表明生物可吸收性涂层补片的浸提液对鼠伤寒沙门氏菌受试株无致突变性;体外哺乳动物细胞染色体畸变试验中,任一处理组的细胞生长率均与阴性对照处于同一水平,表明没有诱导哺乳动物体细胞产生染色体畸变。