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Influence of methylxanthines on chemical mutagenesis and carcinogenesis
292
57 Blagoeva, P., R. Balansky and Z. Mircheva, Laboratory of Chemical Carcinogenesis, National Centre of Oncology, Sofia (Bulgaria)
Influence of methyixanthines on chemical mutagenesis and carcinogenesis Employing the liquid suspension modification of the standard Salmonella/microsome mutagenicity assay, a significant potentiation of N-nitrosoN'-methylurea (MNU)- or N-methyl-N'-nitro-Nnitrosoguanidine (MNNG)-induced mutagenesis was established in S. typhimurium TA1535 grown for 4 h in a nutrient broth containing 10 - 3 M 1,3,7-trimethylxanthine (caffeine). However, added during or after mutagen exposure, caffeine diminished the number of his + revertants by 25-71%. The mutagenic activity of aflatoxin B 1 or benzo[a]pyrene in S. typhimurium TA98 was not influenced significantly by caffeine. Furthermore, a marked stimulation of the chromosome-damaging effect of MNNG was established in CHO cells pre- or post-treated with caffeine. Caffeine (75 or 100 m g / k g b.w., i.p.) potentiated the genotoxic activity of mitomycin C, cyclophosphamide and urethane, established with the micronucleus test in mouse bone marrow. Under the same conditions 1,3-dimethylxanthine (theophylline) inhibited the genotoxic activity of the 2 drugs by up to 30%. Theophylline and caffeine (600 ppm, in drinking water), but not 1-isobutyl-l-methylxanthine inhibited N-nitrosodiethylamine (NDE)-induced hepatocarcinogenesis in rats by 30-63% without influencing the yield of tumours in the oesophagus. Caffeine failed to influence the colon carcinogenesis induced in rats by dimethylhydrazine (DMH). The methylxanthines merit further investigation aimed at evaluating their significance in chemical mutagenesis and carcinogenesis.
58 Chankova, S., K. Vinarova, S. Nikolov, A. Mechandgiev, D. Angelov l, E. Keskinova 1, S. Sergeeva z, S. Ptitsina 2, A. Syomov 2 and V. Shevchenko 2, Institute of Genetics, Bulgarian Academy of Sciences, Sofia (Bulgaria), a Institute of Physics of Solid States, Bulgarian Academy of
Sciences, Sofia (Bulgaria) and : Institute of General Genetics, Academy of Sciences of the U.S.S.R., Moscow (U.S.S.R.)
Some aspects of the investigation into the mechanisms of radioresistance in plants The following 3 strains of Chlorella vulgaris varying in their radioresistance were used in this work: 8/1, 13/R, and 2 3 / R , with respective LD75 of 95, 98, and 220 Gy. Strains 1 3 / R and 2 3 / R were obtained when the wild strain 8/1 was chronically treated with niphimycin. The radioresistant strains were shown to have a greater capacity for photoreactivation of the pyrimidine dimers induced by laser UV-irradiation. The efficiency of ,/-induced single-strand DNA-break repair was found to be identical in all strains studied. At the same time strains 1 3 / R and 23/R were found to have an increased level of endogenic thiols. Study of the ultrastructure of the analyzed strains revealed that strain 2 3 / R has an increased size of pyrenoid and in some cases it may even have 2 pyrenoids. The results obtained imply that the observed radioresistance of the strains under study may be conditioned not only by the efficiency of the repair systems of the DNA breaks but, to a greater extent, by the content of endogenic protectors and, probably, by some ultrastructural changes.
59 De Meester, C., and C. Vervaet, Unit6 de Mutagen+se et de Trratogenrse, Facult6 de M~decine, Universit~ Catholique de Louvain - UCL/72.37, 1200 Brussels (Belgium)
Relationships between chemical structure and antimutagenic activity of l~-carboline compounds Beta-carboline compounds are commonly found in plants, produced in vivo or by heat treatment of tryptophan and casein. Interest in /~-carbolineg results from the finding that compounds such as harman (H) or norharman (N-AN) can modulate the in vitro mutagenicity of different promutagens like Trp-P-2, B(a)P or DAB, and that this effect closely depends on the amount of metabolic activating system. Investigations on monoamine oxidase inhibition revealed that the inhibitory ef-
57 Blagoeva, P., R. Balansky and Z. Mircheva, Laboratory of Chemical Carcinogenesis, National Centre of Oncology, Sofia (Bulgaria)
Influence of methyixanthines on chemical mutagenesis and carcinogenesis Employing the liquid suspension modification of the standard Salmonella/microsome mutagenicity assay, a significant potentiation of N-nitrosoN'-methylurea (MNU)- or N-methyl-N'-nitro-Nnitrosoguanidine (MNNG)-induced mutagenesis was established in S. typhimurium TA1535 grown for 4 h in a nutrient broth containing 10 - 3 M 1,3,7-trimethylxanthine (caffeine). However, added during or after mutagen exposure, caffeine diminished the number of his + revertants by 25-71%. The mutagenic activity of aflatoxin B 1 or benzo[a]pyrene in S. typhimurium TA98 was not influenced significantly by caffeine. Furthermore, a marked stimulation of the chromosome-damaging effect of MNNG was established in CHO cells pre- or post-treated with caffeine. Caffeine (75 or 100 m g / k g b.w., i.p.) potentiated the genotoxic activity of mitomycin C, cyclophosphamide and urethane, established with the micronucleus test in mouse bone marrow. Under the same conditions 1,3-dimethylxanthine (theophylline) inhibited the genotoxic activity of the 2 drugs by up to 30%. Theophylline and caffeine (600 ppm, in drinking water), but not 1-isobutyl-l-methylxanthine inhibited N-nitrosodiethylamine (NDE)-induced hepatocarcinogenesis in rats by 30-63% without influencing the yield of tumours in the oesophagus. Caffeine failed to influence the colon carcinogenesis induced in rats by dimethylhydrazine (DMH). The methylxanthines merit further investigation aimed at evaluating their significance in chemical mutagenesis and carcinogenesis.
58 Chankova, S., K. Vinarova, S. Nikolov, A. Mechandgiev, D. Angelov l, E. Keskinova 1, S. Sergeeva z, S. Ptitsina 2, A. Syomov 2 and V. Shevchenko 2, Institute of Genetics, Bulgarian Academy of Sciences, Sofia (Bulgaria), a Institute of Physics of Solid States, Bulgarian Academy of
Sciences, Sofia (Bulgaria) and : Institute of General Genetics, Academy of Sciences of the U.S.S.R., Moscow (U.S.S.R.)
Some aspects of the investigation into the mechanisms of radioresistance in plants The following 3 strains of Chlorella vulgaris varying in their radioresistance were used in this work: 8/1, 13/R, and 2 3 / R , with respective LD75 of 95, 98, and 220 Gy. Strains 1 3 / R and 2 3 / R were obtained when the wild strain 8/1 was chronically treated with niphimycin. The radioresistant strains were shown to have a greater capacity for photoreactivation of the pyrimidine dimers induced by laser UV-irradiation. The efficiency of ,/-induced single-strand DNA-break repair was found to be identical in all strains studied. At the same time strains 1 3 / R and 23/R were found to have an increased level of endogenic thiols. Study of the ultrastructure of the analyzed strains revealed that strain 2 3 / R has an increased size of pyrenoid and in some cases it may even have 2 pyrenoids. The results obtained imply that the observed radioresistance of the strains under study may be conditioned not only by the efficiency of the repair systems of the DNA breaks but, to a greater extent, by the content of endogenic protectors and, probably, by some ultrastructural changes.
59 De Meester, C., and C. Vervaet, Unit6 de Mutagen+se et de Trratogenrse, Facult6 de M~decine, Universit~ Catholique de Louvain - UCL/72.37, 1200 Brussels (Belgium)
Relationships between chemical structure and antimutagenic activity of l~-carboline compounds Beta-carboline compounds are commonly found in plants, produced in vivo or by heat treatment of tryptophan and casein. Interest in /~-carbolineg results from the finding that compounds such as harman (H) or norharman (N-AN) can modulate the in vitro mutagenicity of different promutagens like Trp-P-2, B(a)P or DAB, and that this effect closely depends on the amount of metabolic activating system. Investigations on monoamine oxidase inhibition revealed that the inhibitory ef-