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Genes and environment : the official journal of the Japanese Environmental Mutagen Society
Jul 16, 2021;43 (1): 30.

In vivo and in vitro mutagenicity of perillaldehyde and cinnamaldehyde.

Masamitsu Honma, Masami Yamada, Manabu Yasui, Katsuyoshi Horibata, Kei-Ichi Sugiyama, Kenichi Masumura
Author Information
  1. Masamitsu Honma: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 3-2-26 Tonomachi, Kawasaki City, Kanagawa, 210-9501, Japan. honma@nihs.go.jp. ORCID
  2. Masami Yamada: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 3-2-26 Tonomachi, Kawasaki City, Kanagawa, 210-9501, Japan.
  3. Manabu Yasui: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 3-2-26 Tonomachi, Kawasaki City, Kanagawa, 210-9501, Japan.
  4. Katsuyoshi Horibata: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 3-2-26 Tonomachi, Kawasaki City, Kanagawa, 210-9501, Japan.
  5. Kei-Ichi Sugiyama: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 3-2-26 Tonomachi, Kawasaki City, Kanagawa, 210-9501, Japan.
  6. Kenichi Masumura: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 3-2-26 Tonomachi, Kawasaki City, Kanagawa, 210-9501, Japan.
PMID: 34271990 DOI: 10.1186/s41021-021-00204-3

Abstract

BACKGROUND: Perillaldehyde and cinnamaldehyde are natural substances found in plants that are used as flavoring ingredients. Due to the α,β-unsaturated aldehydes in their structures, these compounds are expected to be DNA reactive. Indeed, several reports have indicated that perillaldehyde and cinnamaldehyde show positive in in vitro and in vivo genotoxicity tests. However, their genotoxic potentials are currently disputed. To clarify the mutagenicity of perillaldehyde and cinnamaldehyde, we conducted in silico quantitative structure-activity relationship (QSAR) analysis, in vitro Ames tests, and in vivo transgenic rodent gene mutation (TGR) assays.
RESULTS: In Ames tests, perillaldehyde was negative and cinnamaldehyde was positive; these respective results were supported by QSAR analysis. In TGR assays, we treated Muta™ Mice with perillaldehyde and gpt-delta mice with cinnamaldehyde up to the maximum tested doses (1000 mg/kg/day). There was no increase in gene mutations in the liver, glandular stomach, or small intestine following all treatments except the positive control (N-ethyl-N-nitrosourea at 100 mg/kg/day).
CONCLUSIONS: These data clearly show no evidence of in vivo mutagenic potentials of perillaldehyde and cinnamaldehyde (administered up to 1000 mg/kg/day) in mice; however, cinnamaldehyde is mutagenic in vitro.

Keywords

Ames test Cinnamaldehyde Mutagenicity Perillaldehyde Quantitative structure–activity relationship Transgenic rodent gene mutation assay

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Grants

  1. H30-Food-General-003/Ministry of Health, Labour and Welfare
  2. H30-Chemistry-Destination-005/Ministry of Health, Labour and Welfare
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