Potassium octatitanate fibers induce persistent lung and pleural injury and are possibly carcinogenic in male Fischer 344 rats

被引：13

作者：

Abdelgied, Mohamed ^{[1
,2
,3
]}

El-Gazzar, Ahmed M. ^{[1
,2
,4
]}

Alexander, David B. ^{[1
]}

Alexander, William T. ^{[1
]}

Numano, Takamasa ^{[1
]}

Iigou, Masaaki ^{[1
]}

Naiki-Ito, Aya ^{[2
]}

Takase, Hirotsugu ^{[5
]}

Abdou, Khaled Abbas ^{[3
]}

Hirose, Akihiko ^{[6
]}

Taquahashi, Yuhji ^{[7
]}

Kanno, Jun ^{[8
]}

Tsuda, Hiroyuki ^{[1
]}

Takahashi, Satoru ^{[2
]}

机构：

[1] Nagoya City Univ, Nanotoxicol Project, Nagoya, Aichi, Japan

[2] Nagoya City Univ, Dept Expt Pathol & Tumor Biol, Grad Sch Med Sci, Nagoya, Aichi, Japan

[3] Beni Suef Univ, Fac Vet Med, Dept Forens Med & Toxicol, Bani Suwayf, Egypt

[4] Alexandria Univ, Dept Forens Med & Toxicol, Fac Vet Med, Alexandria, Egypt

[5] Nagoya City Univ, Core Lab, Grad Sch Med Sci, Nagoya, Aichi, Japan

[6] Natl Inst Hlth Sci, Div Risk Assessment, Tokyo, Japan

[7] Natl Inst Hlth Sci, Div Cellular & Mol Toxicol, Tokyo, Japan

[8] Japan Ind Safety & Hlth Assoc, Japan Bioassay Res Ctr, Hadano, Kanagawa, Japan

来源：

CANCER SCIENCE | 2018年 / 109卷 / 07期

关键词：

inhalation toxicity; potassium octatitanate fiber; rat; titanium dioxide nanoparticle; trans-tracheal intrapulmonary spraying; INHALATION TOXICITY; PULMONARY RESPONSES; CARBON NANOTUBES; INORGANIC FIBERS; GENE-EXPRESSION; CAVITY; MACROPHAGES; CLEARANCE; ASBESTOS; WHISKERS;

D O I：

10.1111/cas.13643

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Potassium octatitanate fibers (K2O<bold></bold>8TiO(2), POT fibers) are widely used as an alternative to asbestos. We investigated the pulmonary and pleural toxicity of POT fibers with reference to 2 non-fibrous titanium dioxide nanoparticles (nTiO(2)), photoreactive anatase (a-nTiO(2)) and inert rutile (r-nTiO(2)). Ten-week-old male F344 rats were given 0.5 mL of 250 g/mL suspensions of POT fibers, a-nTiO(2), or r-nTiO(2), 8 times (1 mg/rat) over a 15-day period by trans-tracheal intrapulmonary spraying (TIPS). Rats were killed at 6 hours and at 4 weeks after the last TIPS dose. Alveolar macrophages were significantly increased in all treatment groups at 6 hours and at 4 weeks. At week 4, a-nTiO(2) and r-nTiO(2) were largely cleared from the lung whereas a major fraction of POT fibers were not cleared. In the bronchoalveolar lavage, alkaline phosphatase activity was elevated in all treatment groups, and lactate dehydrogenase (LDH) activity was elevated in the a-nTiO(2) and POT groups. In lung tissue, oxidative stress index and proliferating cell nuclear antigen (PCNA) index were elevated in the a-nTiO(2) and POT groups, and there was a significant elevation in C-C motif chemokine ligand 2 (CCL2) mRNA and protein in the POT group. In pleural cavity lavage, total protein was elevated in all 3 treatment groups, and LDH activity was elevated in the a-nTiO(2) and POT groups. Importantly, the PCNA index of the visceral mesothelium was increased in the POT group. Overall, POT fibers had greater biopersistence, induced higher expression of CCL2, and provoked a stronger tissue response than a-nTiO(2) or r-nTiO(2).

引用

页码：2164 / 2177

页数：14

共 36 条

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