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急性有机磷中毒患者染色体DNA损伤、细胞毒性、细胞生长抑制、氧化性DNA损伤及其与内分泌激素关系的评估

Evaluation of chromosomal DNA damage, cytotoxicity, cytostasis, oxidative DNA damage and their relationship with endocrine hormones in patients with acute organophosphate poisoning.

作者信息

Gundogan Kursat, Donmez-Altuntas Hamiyet, Hamurcu Zuhal, Akbudak Ismail Hakkı, Sungur Murat, Bitgen Nazmiye, Baskol Gulden, Bayram Fahri

机构信息

Intensive Care Unit, Department of Internal Medicine, Medical Faculty, Erciyes University, Kayseri, Turkey.

Department of Medical Biology, Medical Faculty, Erciyes University, Kayseri, Turkey.

出版信息

Mutat Res Genet Toxicol Environ Mutagen. 2018 Jan;825:1-7. doi: 10.1016/j.mrgentox.2017.11.005. Epub 2017 Nov 9.

Abstract

Pesticides are commonly used compounds in agriculture. Especially, organophosphates (OPs) are among the extensively used pesticides. Therefore, OPs poisoning is common, especially in underdeveloped and developing countries. Primary aim of this study was to research the effects of acute OPs poisoning on genome instability in the individuals' lymphocytes with acute OPs poisoning both by using the cytokinesis-block micronucleus cytome (CBMN-cyt) assay to examine chromosome/genome damage, cell proliferation index and cell death rate and by using the plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels to determine oxidative DNA damage. Secondary aim of this study was also to assess whether a relation exists between endocrine hormones and the genome damage in acute OPs poisoning. In the study, blood samples were analysed of 13 patients before and after treatment admitted to the Department of Intensive Care Unit with acute OPs poisoning and of 13 healthy subjects of similar age and sex. The present study demonstrates that genome damage (micronucleus; MN and nucleoplasmic bridges; NPBs frequencies), apoptotic and necrotic cell frequencies increased in lymphocytes of patients with acute OPs poisoning before treatment and decreased after treatment. The present study also show that CBMN cyt assay parameters and 8-OHdG levels could be affected by some endocrine hormones such as E2, fT3, fT4, GH, IGF-1, FSH, LH, TSH, PRL, but not be related to ACTH and tT levels in acute OPs poisoning. In conclusion, it is believed that this is the first study to evaluate the chromosomal/oxidative DNA damage, cell proliferation, cell death and their associations with endocrine hormones in acute OPs poisoning. These preliminary findings need to be supported by further studies with larger sample sizes.

摘要

农药是农业中常用的化合物。特别是有机磷酸酯类(OPs)是广泛使用的农药之一。因此,OPs中毒很常见,尤其是在不发达国家和发展中国家。本研究的主要目的是通过使用胞质分裂阻滞微核细胞法(CBMN-cyt)检测来研究急性OPs中毒对急性OPs中毒个体淋巴细胞基因组不稳定性的影响,以检测染色体/基因组损伤、细胞增殖指数和细胞死亡率,并通过检测血浆8-羟基-2'-脱氧鸟苷(8-OHdG)水平来确定氧化性DNA损伤。本研究的次要目的还包括评估急性OPs中毒时内分泌激素与基因组损伤之间是否存在关联。在该研究中,分析了13例急性OPs中毒入住重症监护病房患者治疗前后的血样,以及13例年龄和性别相似的健康受试者的血样。本研究表明,急性OPs中毒患者治疗前淋巴细胞中的基因组损伤(微核;MN和核质桥;NPBs频率)、凋亡和坏死细胞频率增加,治疗后降低。本研究还表明,在急性OPs中毒中,CBMN细胞检测参数和8-OHdG水平可能受某些内分泌激素如E2、游离T3、游离T4、生长激素、胰岛素样生长因子-1(IGF-1)、促卵泡激素(FSH)、促黄体生成素(LH)、促甲状腺激素(TSH)、催乳素(PRL)的影响,但与促肾上腺皮质激素(ACTH)和总甲状腺素(tT)水平无关。总之,据信这是第一项评估急性OPs中毒时染色体/氧化性DNA损伤、细胞增殖、细胞死亡及其与内分泌激素关联的研究。这些初步发现需要通过更大样本量的进一步研究来支持。

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