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Forestomach tumor induction by 2,4-hexadienal in F344N rats and B6C3F1 mice

  • Organ Toxicity and Mechanisms
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Abstract

2,4-Hexadienal (2,4-Hx) was studied for its toxicity and carcinogenicity because of its α, β-unsaturated aldehyde structure and potential link between exposure to lipid peroxidation products in the diet and human malignancies. Male and female F344N rats and B6C3F1 mice received 2,4-Hx in corn oil by gavage for 16 days, 14 weeks, or 2 years. In the 16-day studies 2,4-Hx induced forestomach necrosis and ulceration at 240 mg/kg and forestomach epithelial hyperplasia at 80 mg/kg in rats and mice. In the 14-week studies the chemical induced forestomach hyperplasia and nasal olfactory atrophy or necrosis at 120 mg/kg in rats and mice. In the 2-year studies 2,4-Hx induced squamous cell papilloma and carcinoma of the forestomach in male and female rats at 45 and 90 mg/kg and in male and female mice at 120 mg/kg. Two male mice in the 120 mg/kg group had uncommon squamous cell carcinoma of the oral cavity (tongue). Mechanistic studies indicated that the forestomach carcinogenesis in rats and mice may be due to depletion of glutathione as a result of oxidative stress induced by 2,4-Hx.

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Acknowledgements

These experiments complied with the currents laws of the United States where they were conducted. The authors gratefully acknowledge Ms. JoAnne Johnson, Drs. Kamal Abdo, and Rick Irwin from the NIEHS for their critical review of the manuscript and Norris Flagler for his expertise in preparation of the illustrations.

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Authors and Affiliations

  1. National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, 27709, USA

    Po C. Chan, Joel Mahler, Shyamal Peddada & Abraham Nyska

  2. Institute of Life Science Faculty, Bar-Ilan University, Ramat-Gan, 52900, Israel

    Liat Lomnitski

Authors
  1. Po C. Chan
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  2. Joel Mahler
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  3. Shyamal Peddada
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  4. Liat Lomnitski
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  5. Abraham Nyska
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Correspondence to Po C. Chan.

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Chan, P.C., Mahler, J., Peddada, S. et al. Forestomach tumor induction by 2,4-hexadienal in F344N rats and B6C3F1 mice. Arch Toxicol 77, 511–520 (2003). https://doi.org/10.1007/s00204-003-0481-8

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  • DOI: https://doi.org/10.1007/s00204-003-0481-8

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