大鼠气管内肺部给药 2 周后的长期研究表明,富勒烯和富勒烯晶须不会对肺部和胸膜产生致癌作用

IF 4.8 2区 医学 Q1 TOXICOLOGY Archives of Toxicology Pub Date : 2024-09-13 DOI:10.1007/s00204-024-03863-7
Asraful Nahar Sheema, Aya Naiki-Ito, Anna Kakehashi, Omnia Hosny Mohamed Ahmed, David B. Alexander, William T. Alexander, Takamasa Numano, Hiroyuki Kato, Yuko Goto, Hiroshi Takase, Akihiko Hirose, Takatsugu Wakahara, Kun’ichi Miyazawa, Satoru Takahashi, Hiroyuki Tsuda
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引用次数: 0

摘要

富勒烯晶须(FLW)是由 C60 和 C70 富勒烯(FL)组成的细棒状结构。富勒烯晶须的形状表明其具有潜在的毒性作用,包括对肺部和胸膜的致癌性,类似于石棉和多壁碳纳米管(MWCNT)的致癌作用。然而,目前尚未对 FL 或 FLW 进行长期致癌研究。在本研究中,我们调查了 FL 和 FLW 的肺部和胸膜致癌性。通过气管内肺内喷射(TIPS)给 12 周大的雄性 F344 大鼠注射 0.25 或 0.5 毫克 FL、FLW、MWCNT-7 和 MWCNT-N。在 8 次/15 天 TIPS 给药后的 1 周和 104 周,对急性肺部病变和致癌性进行了分析。在第 1 周,FLW、MWCNT-7 和 MWCNT-N 显著增加了肺泡巨噬细胞浸润。施用 MWCNT-7 和 MWCNT-N 能显著增加 Ccl2 和 Ccl3 的表达、活性氧的产生和细胞增殖,而 FL 或 FLW 则不能。在第 104 周,MWCNT-7 和 MWCNT-N 组的支气管肺泡腺瘤和腺癌发病率显著增加,MWCNT-7 组的间皮瘤发病率显著增加。FL 组和 FLW 组未观察到肺或胸膜肿瘤发生的明显诱导。肺泡上皮细胞中 8-OHdG 阳性细胞的数量在 MWCNT-7 组和 MWCNT-N 组中显著增加,而在 FL 组或 FLW 组中没有增加。在我们的研究中,FL 和 FLW 不具有肺或胸膜致癌性。此外,氧化 DNA 损伤与 MWCNT 诱导的肺癌发生有关,这表明它可能是致癌的一个有用的初始标记。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Fullerene and fullerene whisker are not carcinogenic to the lungs and pleura in rat long-term study after 2-week intra-tracheal intrapulmonary administration

Fullerene whiskers (FLW)s are thin rod-like structures composed of C60 and C70 fullerene (FL). The shape of FLWs suggests potential toxic effects including carcinogenicity to the lung and pleura, similar to effects elicited by asbestos and multi-walled carbon nanotubes (MWCNT)s. However, no long-term carcinogenic studies of FL or FLW have been conducted. In the present study we investigated the pulmonary and pleural carcinogenicity of FL and FLW. Twelve-week-old male F344 rats were administered 0.25 or 0.5 mg FL, FLW, MWCNT-7, and MWCNT-N by intra-tracheal intra-pulmonary spraying (TIPS). Acute lung lesions and carcinogenicity were analyzed at 1 and 104 weeks after 8 doses/15 days TIPS administration. At week 1, FLW, MWCNT-7, and MWCNT-N significantly increased alveolar macrophage infiltration. Expression of Ccl2 and Ccl3, reactive oxygen species production, and cell proliferation were significantly increased by administration of MWCNT-7 and MWCNT-N but not FL or FLW. At week 104, the incidence of bronchiolo-alveolar adenoma plus adenocarcinoma was significantly increased in the MWCNT-7 and MWCNT-N groups, and the incidence of mesothelioma was significantly increased in the MWCNT-7 group. No significant induction of pulmonary or pleural tumorigenesis was observed in the FL or FLW groups. The number of 8-OHdG-positive cells in the alveolar epithelium was significantly increased in the MWCNT-7 and MWCNT-N groups but not in the FL or FLW groups. FL and FLW did not exert pulmonary or pleural carcinogenicity in our study. In addition, oxidative DNA damage was implicated in MWCNT-induced lung carcinogenesis, suggesting that it may be a useful initial marker of carcinogenicity.

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来源期刊
Archives of Toxicology
Archives of Toxicology 医学-毒理学
CiteScore
11.60
自引率
4.90%
发文量
218
审稿时长
1.5 months
期刊介绍: Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.
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