Open AccessMWCNT ‐7 administered to the lung by intratracheal instillation induces development of pleural mesothelioma in F344 rats
Author(s) -
Numano Takamasa,
Higuchi Hitomi,
Alexander David B.,
Alexander William T.,
Abdelgied Mohamed,
ElGazzar Ahmed M.,
Saleh Dina,
Takase Hiroshi,
Hirose Akihiko,
NaikiIto Aya,
Suzuki Shugo,
Takahashi Satoru,
Tsuda Hiroyuki
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14121
Subject(s) - mesothelioma , medicine , lung , intratracheal instillation , intraperitoneal injection , inhalation , asbestos , pathology , pleural cavity , anesthesia , surgery , bronchoalveolar lavage , materials science , metallurgy
Abstract Multi‐walled carbon nanotube‐7 ( MWCNT ‐7) fibers are biopersistent and have a structure similar to asbestos. MWCNT ‐7 has been shown to induce malignant mesothelioma when administered by intrascrotal or intraperitoneal injection in rats and mice, and an inhalation study demonstrated that rats exposed to respirable MWCNT ‐7 developed lung tumors. MWCNT ‐N, which is similar to MWCNT ‐7, was shown to induce both lung tumors and malignant mesothelioma in rats when administered by trans‐tracheal intrapulmonary spraying ( TIPS ). The present study was performed to investigate the carcinogenicity of MWCNT ‐7 when administered by the TIPS method. Ten‐week‐old male F344/Crj rats were divided into 3 groups and administered 0.5 mL vehicle, 0.250 μg/ mL MWCNT ‐7 or 0.250 μg/ mL crocidolite once a week for 12 weeks (total doses of 1.5 mg/rat) and then observed for up to 104 weeks. Rats in the MWCNT ‐7 group began to die from pathologies associated with the development of malignant mesothelioma 35 weeks after the final TIPS administration. Overall, the incidence of malignant mesothelioma in the MWCNT ‐7 group was significantly higher than in the vehicle or crocidolite groups.