Summary
Two new γ-carboline derivatives, 3-amino-1,4-dimethyl-5H pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H pyrido[4,3-b]indole (Trp-P-2), isolated from the pyrolysis products of tryptophan, were found to be potent mutagens. When weanling rats were injected with Trp-P-1 and then given diet containing phenobarbital, they developed enzyme-altered islands in the liver. Since these islands are considered to be formed by immediate progeny of “initiated cells” and cell precursors in hepatocarcinogenesis, Trp-P-1 may well be carcinogenic in rat liver.
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Akimoto, H., Kawai, A., Nomura, H., Nagao, M., Kawachi, T., Sugimura, T.: Synthesis of potent mutagens in tryptophan pyrolysates. Chemistry Letters, 1061–1064 (1977)
Cayama, E., Tsuda, H., Sarma, D.S., Farber, E.: Initiation of chemical carcinogenesis requires cell proliferation. Nature 275, 60–62 (1978)
Higgins, G.M., Anderson, R.M.: Experimental pathology of the liver. I. Restoration of the liver of the white rat following partial surgical removal. Arch. Path: 12, 186–202 (1931)
Ishikawa, T., Takayama, S., Kitagawa, T., Kawachi, T., Kinebuchi, M., Matsukura, N., Uchida, E., Sugimura, T.: In vivo experiments on tryptophan pyrolysis products: In: Miller, E.C., Miller, J.A., Sugimura, T., Takayama, S., Hirono, I. (eds): Naturally Occurring Carcinogens-mutagens and Modulators of Carcinogenesis. Tokyo/Univ.: Baltimore: Japan Scientific Societies Press. Tokyo/Univ.: Park Press, 1979 (in press)
Kitagawa, T., Sugano, H.: Enhancing effect of phenobarbital on the development of enzyme-altered islands and hepatocellular carcinomas initiated by 3′-methyl-4-(dimethylamino) azobenzene or diethylnitrosamine. Gann. 69, 679–687 (1978)
Kitagawa, T., Pitot, H.C., Miller, E.C., Miller, J.A.: Promotion by dietary phenobarbital of hepatocarcinogeneiss by 2-methyl-N,N-dimethyl-4-amino azobenzene in the rat. Cancer Res. 39, 112–115 (1979)
Nagao, M., Honda, M., Seino, Y., Yahagi, T., Sugimura, T.: Mutagenicities of smoke condensates and the charred surface of fish and meat. Cancer Letters 2, 221–226 (1977a)
Nagao, M., Honda, M., Seino, Y., yahagi, T., Kawachi, T., Sugimura, T.: Mutagenicities of protein pyrolysates. Cancer Letters 2, 335–340 (1977b)
Peraino, C., Fry, R.J.M., Staffeld, E., Kisieleski, W.E.: Effects of varying the exposure to phenobarbital on its enhancement of 2-acetylaminofluorene-induced hepatic tumorigenesis in the rat. Cancer Res. 33, 2701–2705 (1973)
Pitot, H.C., Barsness, L., Goldsworthy, T., Kitagawa, T.: Biochemical characterisation of stages of hepatocarcinogenesis after a single dose of diethylnitrosamine. Nature 271, 456–457 (1978)
Scherer, E., Emmelot, P.: Kinetics of induction and growth of precancerous liver-cell foci, and liver tumor formation by diethylnitrosamine in the rat. Eur. J. Cancer 11, 689–696 (1975)
Sugimura, T., Kawachi, T., Nagao, M., Yahagi, T., Seino, Y., Okamoto, T., Shudo, K., Kosuge, T., Tsuji, K., Wakabayashi, K., Iitaka, Y., Itai, A.: Mutagenic principle(s) in tryptophan and phenylalanine pyrolysis products. Proc. Jap. Acad. 53, 58–61 (1977a)
Sugimura, T., Kawachi, T., Nagao, M., Yahagi, T., Seino, Y., Okamoto, T., Shudo, K., Kosuge, T., Matsushima, T., Shirai, A., Sawamura, M., Matsumoto, H.: Mutagencarcinogens in food, with special reference to highly mutagenic pyrolytic products in broiled food.: In: Hiatt, H.H., Watson, J.D., Winsten, J.A. (eds): Origins of Human Cancer, pp. 1561–1577. Cold Spring Harbor Laboratory 1977b
Takayama, S., Hirakawa, T., Sugimura, T.: Malignant transformation in vitro by tryptophan pyrolysis products. Proc. Jap. Acad. 54, 418–422 (1978)
Wachstein, M., Meisel, E.: Enzyme histochemistry of ethionine-induced liver cirrhosis and hepatoma. J. Histochem. Cytochem. 7, 189–201 (1959)
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This work was supported in part by Grants-in-Aid for Cancer Research from the Ministry of Education, Science and Culture, and the Ministry of Health and Welfare, Japan
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Ishikawa, T., Takayama, S., Kitagawa, T. et al. Induction of enzyme-altered islands in rat liver by tryptophan pyrolysis products. J Cancer Res Clin Oncol 95, 221–224 (1979). https://doi.org/10.1007/BF00410642
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DOI: https://doi.org/10.1007/BF00410642