Inhaled Furan Selectively Damages Club Cells in Lungs of A/J Mice

Alexandru Flaviu Tǎbǎran; M. Gerard O’Sullivan; Donna E. Seabloom; Karin R. Vevang; William E. Smith; Timothy S. Wiedmann; Lisa A. Peterson

doi:10.1177/0192623319869306

Inhaled Furan Selectively Damages Club Cells in Lungs of A/J Mice

Alexandru Flaviu Tǎbǎran, M. Gerard O’Sullivan, Donna E. Seabloom, Karin R. Vevang, William E. Smith, Timothy S. Wiedmann, Lisa A. Peterson

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13 Scopus citations

Abstract

Furan, a possible human carcinogen, is a product of incomplete combustion and is present in cigarette smoke, engine exhaust, and processed food. Oral administration induces liver toxicity and carcinogenesis in F344 rats and B6C3F1 mice. To assess possible adverse effects from inhalation, A/J mice were nose-only exposed for 3 hours to furan (0, 30, 75, 150, 300, or 600 ppmv) and euthanized after 24 hours, 48 hours, or 1 week. Histopathology evaluation revealed bronchiolar club cell necrosis (diffuse, marked) with airway denudation following exposure to 300 and 600 ppmv furan with evidence of club cell regeneration and partial repair after 1 week. Initial signs of hepatotoxicity were observed in the 150 ppmv furan-exposed group. Acute necrosis and mineralization were observed in livers at 24 and 48 hours with hepatocyte regeneration by 1-week postexposure in mice exposed to 300 and 600 ppmv furan; the 300 ppmv exposed group had multifocal mineralization that evoked a mild granulomatous response. Measurement of urinary furan metabolites confirmed that the mice metabolized furan to the toxic intermediate, cis-2-butene-1,4-dial. These observations indicate that inhaled furan is toxic to lungs with club cells as the target as well as liver.

Original language	English (US)
Pages (from-to)	842-850
Number of pages	9
Journal	Toxicologic Pathology
Volume	47
Issue number	7
DOIs	https://doi.org/10.1177/0192623319869306
State	Published - Oct 1 2019

Bibliographical note

Funding Information:
The authors thank Mr Bob Carlson for his assistance with the figures. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Masonic Cancer Center, University of Minnesota and Minnesota Masonic Charities, and a grant from the National Cancer Institute and the Food and Drug Administration Center for Tobacco Products. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the FDA. The Masonic Cancer Center Analytical Biochemistry and Comparative Pathology Shared Resources are funded in part by the National Cancer Institute [P30 CA-77598].

Publisher Copyright:
© The Author(s) 2019.

Keywords

club cells
furan
inhalation
liver toxicity
lung toxicity

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title = "Inhaled Furan Selectively Damages Club Cells in Lungs of A/J Mice",

abstract = "Furan, a possible human carcinogen, is a product of incomplete combustion and is present in cigarette smoke, engine exhaust, and processed food. Oral administration induces liver toxicity and carcinogenesis in F344 rats and B6C3F1 mice. To assess possible adverse effects from inhalation, A/J mice were nose-only exposed for 3 hours to furan (0, 30, 75, 150, 300, or 600 ppmv) and euthanized after 24 hours, 48 hours, or 1 week. Histopathology evaluation revealed bronchiolar club cell necrosis (diffuse, marked) with airway denudation following exposure to 300 and 600 ppmv furan with evidence of club cell regeneration and partial repair after 1 week. Initial signs of hepatotoxicity were observed in the 150 ppmv furan-exposed group. Acute necrosis and mineralization were observed in livers at 24 and 48 hours with hepatocyte regeneration by 1-week postexposure in mice exposed to 300 and 600 ppmv furan; the 300 ppmv exposed group had multifocal mineralization that evoked a mild granulomatous response. Measurement of urinary furan metabolites confirmed that the mice metabolized furan to the toxic intermediate, cis-2-butene-1,4-dial. These observations indicate that inhaled furan is toxic to lungs with club cells as the target as well as liver.",

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note = "Funding Information: The authors thank Mr Bob Carlson for his assistance with the figures. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Masonic Cancer Center, University of Minnesota and Minnesota Masonic Charities, and a grant from the National Cancer Institute and the Food and Drug Administration Center for Tobacco Products. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the FDA. The Masonic Cancer Center Analytical Biochemistry and Comparative Pathology Shared Resources are funded in part by the National Cancer Institute [P30 CA-77598]. Publisher Copyright: {\textcopyright} The Author(s) 2019.",

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AU - Wiedmann, Timothy S.

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N2 - Furan, a possible human carcinogen, is a product of incomplete combustion and is present in cigarette smoke, engine exhaust, and processed food. Oral administration induces liver toxicity and carcinogenesis in F344 rats and B6C3F1 mice. To assess possible adverse effects from inhalation, A/J mice were nose-only exposed for 3 hours to furan (0, 30, 75, 150, 300, or 600 ppmv) and euthanized after 24 hours, 48 hours, or 1 week. Histopathology evaluation revealed bronchiolar club cell necrosis (diffuse, marked) with airway denudation following exposure to 300 and 600 ppmv furan with evidence of club cell regeneration and partial repair after 1 week. Initial signs of hepatotoxicity were observed in the 150 ppmv furan-exposed group. Acute necrosis and mineralization were observed in livers at 24 and 48 hours with hepatocyte regeneration by 1-week postexposure in mice exposed to 300 and 600 ppmv furan; the 300 ppmv exposed group had multifocal mineralization that evoked a mild granulomatous response. Measurement of urinary furan metabolites confirmed that the mice metabolized furan to the toxic intermediate, cis-2-butene-1,4-dial. These observations indicate that inhaled furan is toxic to lungs with club cells as the target as well as liver.

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Inhaled Furan Selectively Damages Club Cells in Lungs of A/J Mice

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