Characterization and identification of 6 mutagens in opium pyrolysates implicated in oesophagel cancer in Iran

M. Friesen, I. K. O'Neill, C. Malaveille, L. Garren, A. Hautefeuille, J. R.P. Cabral, D. Galendo, C. Lasne, M. Sala, I. Chouroulinkov, U. Mohr, V. Turusov, N. E. Day, H. Bartsch

Research output: Contribution to journalArticle

Abstract

Previous epidemiological studies have indicated an association between the ingestion of opium pyrolysates, dietary deficiencies, and a high incidence of oesophageal cancer in subjects in north-east Iran. Laboratory studies have shown that pyrolysates of opium and particularly of morphine, a major opium alkaloid, are highly mutagenic in bacteria and induce sister-chromatid exchanges in mammalian cells after metabolic activation. We now report the ability of these pyrolysates to transform Syrian hamster embryo cells in culture and present some evidence for their carcinogenicity in mice and hamsters following topical, subcutaneous, intratracheal and intragastric administration. 6 of the most abundant mutagenic compounds present in morphine pyrolysate were isolated and purified by high-performance liquid chromatography and characterized by gas chromatography/mass spectrometry and 1H-Fourier transform nuclear magnetic resonance spectroscopy. These hitherto unknown compounds, all containing a hydroxy-phenanthrene moiety, were identified as: 3-methyl-3H-naphth[1,2-e]indol-10-ol; 1,2-dihydro-3-methyl-3H-naphth[1,2-e]indol-10-ol; 6-methylaminophenanthren-3-ol; 2-methylphenanthro[3,4-d][1,3]oxazol-10-ol; 2,3-dimethyl-3H-phenanthro[3,4-d]imidazol-10-ol and 2-methyl-3H-phenanthro[3,4-d]imidazol-10-ol. Mutagenicity in Salmonella typhimurium TA98 of these compounds increased in the order listed, the last compound being 35 times more active than benzo[a]pyrene. The mechanisms, by which these mutagens are formed and metabolically activated are discussed.

Original languageEnglish (US)
Pages (from-to)177-191
Number of pages15
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume150
Issue number1-2
DOIs
StatePublished - Jan 1 1985

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

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    Friesen, M., O'Neill, I. K., Malaveille, C., Garren, L., Hautefeuille, A., Cabral, J. R. P., Galendo, D., Lasne, C., Sala, M., Chouroulinkov, I., Mohr, U., Turusov, V., Day, N. E., & Bartsch, H. (1985). Characterization and identification of 6 mutagens in opium pyrolysates implicated in oesophagel cancer in Iran. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 150(1-2), 177-191. https://doi.org/10.1016/0027-5107(85)90114-9