Assessment of the toxicity and carcinogenicity of double-walled carbon nanotubes in the rat lung after intratracheal instillation: a two-year study.
Assessment of the toxicity and carcinogenicity of double-walled carbon nanotubes in the rat lung after intratracheal instillation: a two-year study.
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气管内滴注双壁碳纳米管对大鼠肺的毒性和致癌性的评估：一项为期两年的研究。
DOI：
10.1186/s12989-022-00469-8
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发表时间：
2022-04-22
影响因子：
10
通讯作者：
Tsuda, Hiroyuki
中科院分区：
文献类型：
--
作者：
Saleh, Dina Mourad;Luo, Shengyong;Ahmed, Omnia Hosny Mohamed;Alexander, David B.;Alexander, William T.;Gunasekaran, Sivagami;El-Gazzar, Ahmed M.;Abdelgied, Mohamed;Numano, Takamasa;Takase, Hiroshi;Ohnishi, Makoto;Tomono, Susumu;Hady, Randa Hussein Abd El;Fukamachi, Katsumi;Kanno, Jun;Hirose, Akihiko;Xu, Jiegou;Suzuki, Shugo;Naiki-Ito, Aya;Takahashi, Satoru;Tsuda, Hiroyuki
考虑到碳纳米管（CNT）的工业应用不断扩大，这些材料的安全评估远远低于需要。很少进行长期的体内研究。这是第一个为期2年的体内研究，以评估双壁碳纳米管（DWCNTs）在肺暴露后大鼠肺和胸膜中的影响。将大鼠分为六组：未处理组、媒介物组、3个DWCNT组（0.12 mg/大鼠、0.25 mg/大鼠和0.5 mg/大鼠）和MWCNT-7（0.5 mg/大鼠）。试验材料通过肺内-肺内喷雾（TIPS）给药，隔日一次，连续15天。观察大鼠，直至处死，不进行进一步处理。DWCNT在大鼠肺中具有生物持久性，并诱导显著的肺部炎症，巨噬细胞计数和趋化细胞因子CCL 2和CCL 3水平显著增加。此外，与溶剂对照组相比，0.5 mg DWCNT治疗组大鼠的肺胶原沉积显著更高。用0.5 mg DWCNT（4/24）处理的大鼠的肺癌发展在统计学上并不高（p = 0.0502）比溶剂对照组（0/25），然而，肺肿瘤发展、细支气管肺泡腺瘤和细支气管肺泡癌的总发生率合并，在用0.5mg DWCNT处理的大鼠的肺中，（7/24）在统计学上高于（p < 0.05）载体对照组（1/25）。值得注意的是，用DWCNT处理的两只大鼠（0.25 mg组中的一只和0.5 mg组中的一只）发生胸膜间皮瘤。然而，这两种病变都发生在胸膜脏层，与给予MWCNT-7的大鼠不同，给予DWCNT的大鼠的胸膜灌洗液中HMGB 1水平未升高。这表明DWCNT处理大鼠中发生间皮瘤的机制与人类无关。我们的结果表明，我们测试的DWCNT纤维在大鼠肺中具有生物持久性，并诱导慢性炎症。用0.5 mg DWCNT处理的大鼠出现胸膜纤维化和肺肿瘤。这些发现表明，至少某些类型的DWCNT是致纤维化和致肿瘤的可能性不容忽视。 在线版本包含补充材料，可通过10.1186/s12989-022-00469-8获取。
Considering the expanding industrial applications of carbon nanotubes (CNTs), safety assessment of these materials is far less than needed. Very few long-term in vivo studies have been carried out. This is the first 2-year in vivo study to assess the effects of double walled carbon nanotubes (DWCNTs) in the lung and pleura of rats after pulmonary exposure. Rats were divided into six groups: untreated, Vehicle, 3 DWCNT groups (0.12 mg/rat, 0.25 mg/rat and 0.5 mg/rat), and MWCNT-7 (0.5 mg/rat). The test materials were administrated by intratracheal-intrapulmonary spraying (TIPS) every other day for 15 days. Rats were observed without further treatment until sacrifice. DWCNT were biopersistent in the rat lung and induced marked pulmonary inflammation with a significant increase in macrophage count and levels of the chemotactic cytokines CCL2 and CCL3. In addition, the 0.5 mg DWCNT treated rats had significantly higher pulmonary collagen deposition compared to the vehicle controls. The development of carcinomas in the lungs of rats treated with 0.5 mg DWCNT (4/24) was not quite statistically higher (p = 0.0502) than the vehicle control group (0/25), however, the overall incidence of lung tumor development, bronchiolo-alveolar adenoma and bronchiolo-alveolar carcinoma combined, in the lungs of rats treated with 0.5 mg DWCNT (7/24) was statistically higher (p < 0.05) than the vehicle control group (1/25). Notably, two of the rats treated with DWCNT, one in the 0.25 mg group and one in the 0.5 mg group, developed pleural mesotheliomas. However, both of these lesions developed in the visceral pleura, and unlike the rats administered MWCNT-7, rats administered DWCNT did not have elevated levels of HMGB1 in their pleural lavage fluids. This indicates that the mechanism by which the mesotheliomas that developed in the DWCNT treated rats is not relevant to humans. Our results demonstrate that the DWCNT fibers we tested are biopersistent in the rat lung and induce chronic inflammation. Rats treated with 0.5 mg DWCNT developed pleural fibrosis and lung tumors. These findings demonstrate that the possibility that at least some types of DWCNTs are fibrogenic and tumorigenic cannot be ignored. The online version contains supplementary material available at 10.1186/s12989-022-00469-8.
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影响因子：
17.1
作者：
Silva, Rona M.;Doudrick, Kyle;Franzi, Lisa M.;TeeSy, Christel;Anderson, Donald S.;Wu, Zheqiong;Mitra, Somenath;Vu, Vincent;Dutrow, Gavin;Evans, James E.;Westerhoff, Paul;Van Winkle, Laura S.;Raabe, Otto G.;Pinkerton, Kent E.
通讯作者：
Pinkerton, Kent E.
影响因子：
7.3
作者：
Dong J;Ma Q
通讯作者：
Ma Q
DOI：
10.1016/j.ijheh.2020.113472
发表时间：
2020-04-01
影响因子：
6
作者：
Canu, I. Guseva;Batsungnoen, K.;Hopf, N. B.
通讯作者：
Hopf, N. B.
Fischer 344（F344）和其他大鼠菌株中自发的原发性胸膜间皮瘤：回顾性综述。
影响因子：
1.5
作者：
Tokarz DA;Gruebbel MM;Willson GA;Hardisty JF;Pearse G;Cesta MF
通讯作者：
Cesta MF
DOI：
10.3390/nano11030745
发表时间：
2021-03-16
期刊：
Nanomaterials (Basel, Switzerland)
影响因子：
--
作者：
Bergamaschi E;Garzaro G;Wilson Jones G;Buglisi M;Caniglia M;Godono A;Bosio D;Fenoglio I;Guseva Canu I
通讯作者：
Guseva Canu I