Polianskaia G G, Sizova L S
Tsitologiia. 1996;38(9):958-73.
The genotoxicity of an antibiotic ciprofloxacin (CF) in doses of 10, 25, 50 and 100 mkg/ml under its short-term (6-48 h) and long-term (15-30 days) action on sublines of Rat kangaroo kidney, NBL-3-11, and Indian muntjak skin fibroblasts has been studied. The emergence of genotoxic effect depends on the dose and time of ciprofloxacin action on both the sublines, but the degree of this effect does not depend on these parameters directly. Ciprofloxacin exerts no influence on cell distribution for chromosome number in subline NBL-3-11, and increases heterogeneity of this parameter in the subline of Indian muntjac skin fibroblasts in 30 days after its addition in doses of 25 and 50 mkg/ml. The degree of increase of chromosomal aberrations in the subline of Indian muntjak skin fibroblasts was in average 1.5 times more than in NBL-3-11 in all examined variants compared to the control. The minimum antibiotic dose that induced chromosomal aberrations was 25 mkg/ml in the subline of NBL-3-11 under a short-term action and 50 mkg/ml under a long-term action. For the subline of Indian muntjac skin fibroblasts the minimum inducing dose was 50 mkg/ml irrespective of the duration of action, except the case of 15 days, when the number of dicentrics increased still at 25 mkg/ml. In both sublines with the duration of ciprofloxacin action within 6-24 h the replacement of chromatid aberrations by chromosomal aberrations occurred. Under a long-term ciprofloxan action differences in types of chromosomal aberrations were discovered: for subline NBL-3-11 these were mainly chromosomal breaks; in the case of muntjac cells both chromosomal breaks and dicentrics (telomeric associations) occurred. The preferential involvement of some chromosomes in dicentric formation was observed. In cells of the muntjac subline, unlike NBL-3-11, the sensitivity of individual chromosomes to ciprofloxacin-induced breaks differed from that to spontaneous breaks. In both the sublines ciprofloxacin induces chromosomal breaks mainly in definite regions of chromosomes. Possible reasons of differences between the examined sublines towards the character of chromosomal instability are discussed in addition to the role of dicentrics as a proposed adaptation of cells to unfavourable factors of the environment.
研究了抗生素环丙沙星(CF)在10、25、50和100微克/毫升剂量下,对大鼠袋鼠肾亚系NBL - 3 - 11和印度麂皮肤成纤维细胞短期(6 - 48小时)和长期(15 - 30天)作用的遗传毒性。遗传毒性效应的出现取决于环丙沙星对两个亚系作用的剂量和时间,但这种效应的程度并不直接取决于这些参数。环丙沙星对NBL - 3 - 11亚系细胞的染色体数目分布没有影响,而在添加25和50微克/毫升剂量的环丙沙星30天后,印度麂皮肤成纤维细胞亚系中该参数的异质性增加。在所有检测变体中,与对照相比,印度麂皮肤成纤维细胞亚系中染色体畸变增加的程度平均比NBL - 3 - 11亚系高1.5倍。在NBL - 3 - 11亚系中,短期作用下诱导染色体畸变的最低抗生素剂量为25微克/毫升,长期作用下为50微克/毫升。对于印度麂皮肤成纤维细胞亚系,除了作用15天的情况(此时25微克/毫升时双着丝粒数量仍增加)外,无论作用持续时间如何,最低诱导剂量均为50微克/毫升。在两个亚系中,当环丙沙星作用持续时间在6 - 24小时内时,染色单体畸变会被染色体畸变取代。在环丙沙星长期作用下,发现了染色体畸变类型的差异:对于NBL - 3 - 11亚系,主要是染色体断裂;对于麂细胞,则同时出现染色体断裂和双着丝粒(端粒关联)。观察到某些染色体在双着丝粒形成中优先受累。在麂亚系细胞中,与NBL - 3 - 11不同,单个染色体对环丙沙星诱导断裂的敏感性与自发断裂的敏感性不同。在两个亚系中,环丙沙星主要在染色体的特定区域诱导染色体断裂。除了双着丝粒作为细胞对不利环境因素的一种拟议适应作用外,还讨论了所检测亚系在染色体不稳定性特征方面存在差异的可能原因。