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乙酰三乙酯柠檬酸酯作为替代增塑剂的遗传毒性和葡萄糖耐量诱导作用与邻苯二甲酸二(2-乙基己基)酯的对比。

Genotoxicity and glucose tolerance induction by acetyltriethylcitrate, substitute plasticizer compared to di(2-ethylhexyl)phthalate.

机构信息

Department of Bioscience and Biotechnology, Sejong University, Seoul, 05006, Republic of Korea.

WOOJUNG BIO Co Ltd, Suwon 16229, Gyeonggi-do, Republic of Korea.

出版信息

Sci Rep. 2019 Aug 22;9(1):12237. doi: 10.1038/s41598-019-48599-y.

Abstract

As di(2-ethylhexyl) phthalate (DEHP), one of phthalates, is classified as probable human carcinogens in EPA, acetyltriethyl citrate(ATEC), one of aliphatic esters, could be applied to DEHP substitute. ATEC is used as plasticizers in cosmetics and nail products. Here, we studied whether ATEC might have genotoxic potential and induce glucose tolerance as compared to DEHP. Genotoxicity was determined by Ames test with histidine-requiring Salmonella typhimurium (TA98, TA100, TA1535 and TA1537) and tryptophan-requiring Escherichia coli (WP2uvrA(pKM101)) strains, chromosomal aberration assay with Chinese hamster lung(CHL/IU) cells, and micronucleus test with bone marrow cells of CD-1 mice. The number of revertants was not significantly changed in Ames test. The frequency of cells with chromosome aberrations was less than 5% in ATEC- or DEHP-treated cells for 6 or 24 h. In addition, no statistically significant increase was observed for the incidence of micronucleated polychromatic erythrocytes (MNPCE) in polychromatic erythrocytes (PCE) and for the ratio of PCE among total erythrocytes at 24 or 48 h after the treatment of mice with ATEC or DEHP. In the meanwhile, blood glucose level (BGL) was increased by the treatment of mice with DEHP or ATEC for 5 consecutive days. Additional 7 days later, BGL by DEHP was recovered to normal level, but not that by ATEC. Then, taken together, our results suggest that ATEC could disrupt glucose metabolism under our experimental conditions. Therefore, although DEHP and ATEC may not be genotoxic, our data should be helpful for persons with the problem in glucose metabolism to choose products containing DEHP or ATEC.

摘要

作为邻苯二甲酸酯(PAEs)中的一种,邻苯二甲酸二(2-乙基己基)酯(DEHP)被美国环保署(EPA)列为可能的人类致癌物质,柠檬酸三乙酯(ATEC)作为一种脂肪族酯类物质,可作为 DEHP 的替代品。ATEC 被用作化妆品和指甲油中的增塑剂。在这里,我们研究了 ATEC 是否可能具有遗传毒性,并与 DEHP 相比诱导葡萄糖耐量。通过含有组氨酸的鼠伤寒沙门氏菌(TA98、TA100、TA1535 和 TA1537)和含有色氨酸的大肠杆菌(WP2uvrA(pKM101))菌株的艾姆斯试验、中国仓鼠肺(CHL/IU)细胞的染色体畸变试验和 CD-1 小鼠骨髓细胞的微核试验来确定遗传毒性。在艾姆斯试验中,回复突变体的数量没有明显变化。在 ATEC 或 DEHP 处理 6 或 24 小时的细胞中,染色体畸变细胞的频率均低于 5%。此外,在 ATEC 或 DEHP 处理小鼠 24 或 48 小时后,多染红细胞(PCE)中的微核多染红细胞(MNPCE)发生率和 PCE 占总红细胞的比值均无统计学意义的增加。同时,DEHP 或 ATEC 处理小鼠 5 天可使血糖水平(BGL)升高。7 天后,DEHP 处理组的 BGL 恢复正常,但 ATEC 处理组的 BGL 未恢复正常。因此,我们的研究结果表明,在我们的实验条件下,ATEC 可能会破坏葡萄糖代谢。因此,尽管 DEHP 和 ATEC 可能没有遗传毒性,但我们的数据可能有助于有葡萄糖代谢问题的人选择含有 DEHP 或 ATEC 的产品。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f1/6706371/70ed71faa518/41598_2019_48599_Fig1_HTML.jpg

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