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Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish.

Abstract

Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been isolated and their structures determined, most being previously unregistered compounds. They are highly mutagenic towards Salmonella typhimurium in the presence of S9 mix and are also mutagenic in vitro and in vivo toward mammalian cells. HCAs have now been chemically synthesized in quantity and subjected to long-term animal testing. When HCAs were fed in the diet, rodents developed cancers in many organs, including the colon, breast and prostate, and one HCA produced hepatomas in monkeys. The lesions exhibited alteration in genes including Apc, beta-catenin and Ha-ras, and these changes provide clues to the induction mechanisms. The HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N-C bonds at guanine bases. There are HCA-sensitive and resistant strains of rodents and a search for the responsible genes is now under way. While the content of HCAs in dishes consumed in ordinary life is low and not sufficient in itself to explain human cancer, the coexistence of many other mutagens/carcinogens of either autobiotic or xenobiotic type and the possibility that HCAs induce genomic instability and heightened sensitivity to tumor promoters suggest that avoidance of exposure to HCAs or reduction of HCAs' biological effects as far as possible are to be highly recommended. Usage of microwave ovens for cooking and supplementation of the diet, for example with soy-isoflavones, which have been found to suppress the occurrence of HCA-induced breast cancers, should be encouraged. Advice to the general public about how to reduce the carcinogenic load imposed by HCAs would be an important contribution to cancer prevention.

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  • Authors+Show Affiliations

    ,

    National Cancer Center, Chuo-ku, Tokyo 104-0045, Japan. tsugimur@gan2.ncc.go.jp

    , ,

    Source

    Cancer science 95:4 2004 Apr pg 290-9

    MeSH

    Amines
    Animals
    Carcinogenicity Tests
    Carcinogens
    Cocarcinogenesis
    Cooking
    DNA Adducts
    DNA Damage
    Dose-Response Relationship, Drug
    Fishes
    Gastrointestinal Neoplasms
    Genetic Predisposition to Disease
    Heterocyclic Compounds
    Hot Temperature
    Humans
    Liver Neoplasms, Experimental
    Meat
    Mice
    Mutagenicity Tests
    Mutagens
    Neoplasms
    Quinolines
    Rats
    Risk

    Pub Type(s)

    Journal Article
    Review

    Language

    eng

    PubMed ID

    15072585

    Citation

    Sugimura, Takashi, et al. "Heterocyclic Amines: Mutagens/carcinogens Produced During Cooking of Meat and Fish." Cancer Science, vol. 95, no. 4, 2004, pp. 290-9.
    Sugimura T, Wakabayashi K, Nakagama H, et al. Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish. Cancer Sci. 2004;95(4):290-9.
    Sugimura, T., Wakabayashi, K., Nakagama, H., & Nagao, M. (2004). Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish. Cancer Science, 95(4), pp. 290-9.
    Sugimura T, et al. Heterocyclic Amines: Mutagens/carcinogens Produced During Cooking of Meat and Fish. Cancer Sci. 2004;95(4):290-9. PubMed PMID: 15072585.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish. AU - Sugimura,Takashi, AU - Wakabayashi,Keiji, AU - Nakagama,Hitoshi, AU - Nagao,Minako, PY - 2004/4/10/pubmed PY - 2004/7/14/medline PY - 2004/4/10/entrez SP - 290 EP - 9 JF - Cancer science JO - Cancer Sci. VL - 95 IS - 4 N2 - Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been isolated and their structures determined, most being previously unregistered compounds. They are highly mutagenic towards Salmonella typhimurium in the presence of S9 mix and are also mutagenic in vitro and in vivo toward mammalian cells. HCAs have now been chemically synthesized in quantity and subjected to long-term animal testing. When HCAs were fed in the diet, rodents developed cancers in many organs, including the colon, breast and prostate, and one HCA produced hepatomas in monkeys. The lesions exhibited alteration in genes including Apc, beta-catenin and Ha-ras, and these changes provide clues to the induction mechanisms. The HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N-C bonds at guanine bases. There are HCA-sensitive and resistant strains of rodents and a search for the responsible genes is now under way. While the content of HCAs in dishes consumed in ordinary life is low and not sufficient in itself to explain human cancer, the coexistence of many other mutagens/carcinogens of either autobiotic or xenobiotic type and the possibility that HCAs induce genomic instability and heightened sensitivity to tumor promoters suggest that avoidance of exposure to HCAs or reduction of HCAs' biological effects as far as possible are to be highly recommended. Usage of microwave ovens for cooking and supplementation of the diet, for example with soy-isoflavones, which have been found to suppress the occurrence of HCA-induced breast cancers, should be encouraged. Advice to the general public about how to reduce the carcinogenic load imposed by HCAs would be an important contribution to cancer prevention. SN - 1347-9032 UR - https://www.unboundmedicine.com/medline/citation/15072585/full_citation L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1347-9032&date=2004&volume=95&issue=4&spage=290 DB - PRIME DP - Unbound Medicine ER -