LACK OF COMBINATION HEPATOCARCINOGENICITY OF HARMAN, NORHARMAN AND AMITROLE WHEN GIVEN WITH NaNO2 IN THE RAT

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  • ICHIHARA Toshio
    DIMS Institute of Medical Science Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences
  • MIYASHITA Kayoko
    DIMS Institute of Medical Science Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences
  • KAWABE Mayumi
    DIMS Institute of Medical Science
  • IMAIDA Katsumi
    Kagawa University Faculty of Medicine, Department of Pathology and Host-Defense, Onco-Pathology
  • ASAMOTO Makoto
    Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences
  • OGISO Tadashi
    Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences
  • TAMANO Seiko
    DIMS Institute of Medical Science
  • HIROSE Masao
    Division of Pathology, National Institute of Health Sciences
  • SHIRAI Tomoyuki
    Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences

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N-Nitrosocompounds, which induce cancers in various organs, may be formed endogenously with intake of amino compounds such as secondary amines and sodium nitrite (NaNO2) in combination. The present study was performed to investigate whether three amino compounds, 1-methyl-9H-pyrido[3,4-b]indole (harman), 9H-pyrido[3,4-b]indole (norharman) and 2-amino-1,3,4-triazole (amitrole), might be converted in vivo to compounds capable of promoting hepatocarcinogenesis when given with NaNO2. However, in an 8-week model, no modifying potential was evident in terms of numbers and areas of putative preneoplastic glutathione S-transferase placental form (GST-P)-positive foci in any of the groups receiving paired treatments. These results demonstrate that combinations of harman, norharman and amitrole with NaNO2 lack promoting effects for liver carcinogenesis in our medium-term bioassay system.<br>

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