Cell proliferation analysis is a reliable predictor of lack of carcinogenicity: Case study using the pyrethroid imiprothrin on lung tumorigenesis in mice

Kensuke Kawamoto, Keiko Ogata, Hiroyuki Asano, Kaori Miyata, Tokuo Sukata, Tooru Utsumi, Samuel M. Cohen, Tomoya Yamada

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

In the mouse carcinogenicity study, an apparent increase in lung adenocarcinoma was observed in male mice at 7000 ppm. Based on the overall evaluation of toxicology, oncology, pathology and statistics, we concluded that the apparent increase in lung tumors is not relevant for evaluation of carcinogenicity of imiprothrin (Regul Toxicol Pharmacol, 105, 1–14, 2019). To investigate whether imiprothrin has any mitogenic effect on mouse Club cells, the present study examined its effects on replicative DNA synthesis of Club cells and lung histopathology in male mice treated with imiprothrin for 7 days at 3500 and 7000 ppm in the diet. Isoniazid, a known mouse lung mitogen and tumor inducer, was also examined at 1000 ppm in the diet as a positive control of Club cell mitogenesis and morphological changes. Neither imiprothrin nor isoniazid caused any necrotic changes in lung by light or electron microscopy. There were no increases observed in the bromodeoxyuridine (BrdU) labeling index in the imiprothrin groups, while there was a statistically significant increase in the BrdU labeling index in the isoniazid group. These findings demonstrate that imiprothrin does not induce mouse Club cell proliferation or morphologic changes, supporting our previous conclusion described above. Thus, imiprothrin should not be classified as a carcinogen. Furthermore, this study indicates that short-term studies focusing on cell proliferation can be reliable for predicting a lack of carcinogenic potential of test chemicals.

Original languageEnglish (US)
Article number104646
JournalRegulatory Toxicology and Pharmacology
Volume113
DOIs
StatePublished - Jun 2020

Keywords

  • Carcinogenicity
  • Club cells
  • Isoniazid
  • Pyrethroid
  • Replicative DNA synthesis
  • Short-term bioassays

ASJC Scopus subject areas

  • Toxicology

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