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五氯苯酚、林丹、七氟菊酯、氯氟氰菊酯和天然除虫菊对人下鼻甲和中鼻甲黏膜细胞的遗传毒性作用。

Genotoxic effects of pentachlorophenol, lindane, transfluthrin, cyfluthrin, and natural pyrethrum on human mucosal cells of the inferior and middle nasal conchae.

作者信息

Tisch Matthias, Faulde Michael K, Maier Heinz

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery, Bundeswehr Hospital, Ulm, Germany.

出版信息

Am J Rhinol. 2005 Mar-Apr;19(2):141-51.

Abstract

BACKGROUND

Animal experiments and epidemiological studies suggest that pentachlorophenol (PCP) and gamma-hexachlorocyclohexane (lindane) should be classified as possible human carcinogens. In the past, both have had a variety of applications in the civilian and military sectors and in forestry. They have, e.g., been used to impregnate and treat uniforms and other fabrics and to control human lice. Animal experiments indicate that PCP in particular causes mutations and chromosome aberrations and thus DNA damage. Studies on whether or not this also applies to newer substances and especially to natural type I and type II pyrethroids still are not available. What is particularly lacking are data on the genotoxic effects of these substances on human target cells. Our study describes the genotoxic effects of PCP, lindane, transfluthrin, cyfluthrin, and natural pyrethrum on human mucosal cells of the inferior and middle nasal conchae.

METHODS

Epithelial cells were isolated from nasal mucosa, which was removed in the surgical treatment of chronic sinusitis and nasal concha hyperplasia. After the cells had been tested for vitality using the trypan blue exclusion test, the short-term culture method was used. The material was incubated with PCP (0.3, 0.75, and 1.2 mmol), lindane (0.5, 0.75, and 1.0 mmol), transfluthrin (0.05, 0.1, 0.5, 0.75, and 1.0 mmol), cyfluthrin (0.05, 0.1, 0.5, 0.75, and 1.0 mmol), natural pyrethrum (0.001, 0.005, 0.01, 0.05, and 0.1 mmol), and N-methyl-N'-nitro-N-nitrosoguanidine for 60 minutes. Substance-induced DNA damage (single-strand and double-strand breaks) were determined using single-cell microgel electrophoresis. A fluorescence microscope was used together with an image processing system to analyze the results obtained.

RESULTS

After exposure to all tested substances, a high percentage of the cells of the middle nasal concha in particular were found to have severely fragmented DNA as a result of strong genotoxic effects. Although the reaction of the cells of the inferior nasal concha was significantly less strong (p < 0.001), the tested substances were nevertheless found to have a notable genotoxic effect on these cells too.

CONCLUSION

Our study strongly suggests that exposure to PCP, lindane, transfluthrin, cyfluthrin, and natural pyrethrum has a genotoxic effect on the epithelial cells of human nasal mucosa. In addition, we have shown that nasal structures differ in susceptibility to the various pesticides used in the tests. Thus, the study provides new evidence supporting the biological plausibility of PCP- and lindane-induced effects, thereby helping evaluate potential PCP- and lindane-induced mucous membrane carcinomas of these parts of the nose. In addition, our study shows that other substances that today are widely used for controlling pests have a considerable genotoxic effect on human target cells. The results obtained indicate the need for additional studies on the genotoxicity of these substances and their adverse effects on human health.

摘要

背景

动物实验和流行病学研究表明,五氯苯酚(PCP)和γ-六氯环己烷(林丹)应被归类为可能的人类致癌物。过去,它们在民用、军事和林业领域都有多种应用。例如,它们被用于浸渍和处理制服及其他织物,以及控制人体虱子。动物实验表明,尤其是五氯苯酚会导致突变和染色体畸变,从而造成DNA损伤。关于这是否也适用于更新的物质,特别是天然I型和II型拟除虫菊酯,目前尚无相关研究。尤其缺乏这些物质对人类靶细胞遗传毒性作用的数据。我们的研究描述了五氯苯酚、林丹、四氟甲醚菊酯、氯氟氰菊酯和天然除虫菊对人下鼻甲和中鼻甲黏膜细胞的遗传毒性作用。

方法

从慢性鼻窦炎和鼻甲增生手术治疗中切除的鼻黏膜中分离上皮细胞。使用台盼蓝排斥试验检测细胞活力后,采用短期培养方法。将材料与五氯苯酚(0.3、0.75和1.2 mmol)、林丹(0.5、0.75和1.0 mmol)、四氟甲醚菊酯(0.05、0.1、0.5、0.75和1.0 mmol)、氯氟氰菊酯(0.05、0.1、0.5、0.75和1.0 mmol)、天然除虫菊(0.001、0.005、0.01、0.05和0.1 mmol)以及N-甲基-N'-硝基-N-亚硝基胍一起孵育60分钟。使用单细胞微凝胶电泳测定物质诱导的DNA损伤(单链和双链断裂)。使用荧光显微镜和图像处理系统分析所得结果。

结果

暴露于所有测试物质后发现,尤其是中鼻甲的细胞中,由于强烈的遗传毒性作用,有很大比例的细胞DNA严重碎片化。尽管下鼻甲细胞的反应明显较弱(p < 0.001),但测试物质对这些细胞仍有显著的遗传毒性作用。

结论

我们的研究强烈表明,接触五氯苯酚、林丹、四氟甲醚菊酯、氯氟氰菊酯和天然除虫菊对人鼻黏膜上皮细胞有遗传毒性作用。此外,我们已经表明,鼻结构对测试中使用的各种农药的敏感性不同。因此,该研究提供了新的证据,支持五氯苯酚和林丹诱导效应的生物学合理性,从而有助于评估五氯苯酚和林丹诱导的这些鼻部区域黏膜癌的可能性。此外,我们的研究表明,如今广泛用于控制害虫的其他物质对人类靶细胞有相当大的遗传毒性作用。所得结果表明需要对这些物质的遗传毒性及其对人类健康的不利影响进行更多研究。

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