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Review
. 2021 Sep 16;43(1):38.
doi: 10.1186/s41021-021-00207-0.

Mutagenicity of carcinogenic heterocyclic amines in Salmonella typhimurium YG strains and transgenic rodents including gpt delta

Affiliations
Review

Mutagenicity of carcinogenic heterocyclic amines in Salmonella typhimurium YG strains and transgenic rodents including gpt delta

Takehiko Nohmi et al. Genes Environ. .

Abstract

Chemical carcinogens to humans have been usually identified by epidemiological studies on the relationships between occupational or environmental exposure to the agents and specific cancer induction. In contrast, carcinogenic heterocyclic amines were identified under the principle that mutagens in bacterial in the Ames test are possible human carcinogens. In the 1970s to 1990s, more than 10 heterocyclic amines were isolated from pyrolysates of amino acids, proteins, meat or fish as mutagens in the Ames test, and they were demonstrated as carcinogens in rodents. In the 1980s and 1990s, we have developed derivatives of the Ames tester strains that overexpressed acetyltransferase of Salmonella typhimurium. These strains such as Salmonella typhimurium YG1024 exhibited a high sensitivity to the mutagenicity of the carcinogenic heterocyclic amines. Because of the high sensitivity, YG1024 and other YG strains were used for various purposes, e.g., identification of novel heterocyclic amines, mechanisms of metabolic activation, comparison of mutagenic potencies of various heterocyclic amines, and the co-mutagenic effects. In the 1990s and 2000s, we developed transgenic mice and rats for the detection of mutagenicity of chemicals in vivo. The transgenics were generated by the introduction of reporter genes for mutations into fertilized eggs of mice and rats. We named the transgenics as gpt delta because the gpt gene of Escherichia coli was used for detection of point mutations such as base substitutions and frameshifts and the red/gam genes of λ phage were employed to detect deletion mutations. The transgenic rodents gpt delta and other transgenics with lacI or lacZ as reporter genes have been utilized for characterization of mutagenicity of heterocyclic amines in vivo. In this review, we summarized the in vitro mutagenicity of heterocyclic amines in Salmonella typhimurium YG strains and the in vivo mutagenicity in transgenic rodents. We discussed the relationships between in vitro and in vivo mutagenicity of the heterocyclic amines and their relations to the carcinogenicity.

Keywords: Acetyltransferase; Ames test; Carcinogenicity; Heterocyclic amines; Mutagenicity; Salmonella typhimurium YG strains; Transgenic; gpt delta.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Gene cloning of the oat gene encoding O-acetyltransferase in Salmonella typhimurium. The chromosome DNA of Salmonella typhimurium TA1538 was partially digested with Sau3A1 and ligated to BamH1-digested plasmid pBR322, thereby generating a plasmid library of TA1538. Then, the library DNA was introduced into Salmonella typhimurium TA1538/1,8-DNP and screened the colonies that could grow on plates without 2-NF but could not grow on plates with 2-NF
Fig. 2
Fig. 2
Protocols of gpt delta transgenic rodent mutation assays. Gpt delta mice or rats are exposed to chemicals by feeding, gavage or others. Then, the genomic DNA is extracted from various organs or tissues to recover λ phage EG10 particles by λ packaging reactions. Then, the rescued phages are introduced to indicator E. coli for gpt selection and for Spi selection that detect point mutations and deletion mutations, respectively. DNA is extracted from 6-TG-resistant colonies or Spi plaques for DNA sequencing

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References

    1. IARC. IARC monographs on the identification of carcinogenic hazards to humans. Lyon: WHO Press. Available from: https://monographs.iarc.who.int/agents-classified-by-the-iarc/
    1. IARC . o-toluidine. Chemical agents and related occupations. IARC Monograph on the Evaluation of Carcinogenic Risks to Humans. 100F. Lyon: WHO Press; 2012. pp. 93–100. - PMC - PubMed
    1. IARC . Asbestos. Arsenic, fibre, metal and dusts, a review of human carcinogens. IARC Monographs on the Evaluation of the Carcinogenic Risks of Chemicals to Humans. 100C. Lyon: WHO Press; 2012. pp. 219–310.
    1. IARC . 1,2-dichloropropane. Some chemicals used as solvents and in polymer manufacture. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 110. WHO Press; 2017. pp. 141–176.
    1. IARC . vinyl chloride. Chemical agents and related occupations. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 100F. Lyon: WHO Press; 2012. pp. 451–478. - PMC - PubMed

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