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

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

doi:10.1007/s00204-024-03863-7

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

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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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. Fullerene and fullerene whisker are not carcinogenic to the lungs and pleura in rat long‑term study after 2‑week intra‑tracheal intrapulmonary administration. ARCHIVES OF TOXICOLOGY. 2024, 98 (), . https://doi.org/10.1007/s00204-024-03863-7

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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 multiwalled 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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