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The use of Aspergillus nidulans as a test system for extranuclear mutations induced by environmental chemicals
180
for malathion (8ppm), 0.026 mg/kg for methyl parathion (0.15 ppm), and 0.09 mg/kg for trichlorfon (0.5 ppm). At the end of the treatment, cytogenetic effects were analysed in bone-marrow cells, spermatogonia, and diakinesis, and genetic effects were investigated in the dominant lethal mutation test. In the 3 cytogenetic systems, the frequency of fragments, exchanges and gaps was not found to be enhanced over the control level. In the dominant lethal mutation test, the results obtained for the frequency of pre-implantation losses, postimplantation deaths, and live embryos per female were within the control limits.
33 Deknudt, Gh., Laboratory of Genetics, Department of Radiobiology, S.C.K.-C.E.N., B-2400 Mol (Belgium) In vivo study of the mutagenicity of heavy metals in mammals
The dominant lethal test has been performed over a period of 5 weeks to study in BALB/c mice the mutagenic activity of 2 chromium compounds, potassium dichromate (K2Cr2OT) and calcium chromate (CaCrO4) and 2 nickel compounds, nickel nitrate (Ni(NO3) 2) and nickel chloride (NiC12). The doses were chosen on the basis of a preliminary experiment and correspond roughly to one half of the LDs000): K2CrO 7, 20 mg/kg; Ni(NO3) 2, 56 mg/kg; NiC12, 25 mg/kg. Due to the low solubility of the compound, an 8-fold lower concentration of CaCrO4 (40 mg/kg) was used. The chromium and nickel compounds produced a significant reduction in the rate of pregnancies. Furthermore, a lower incidence of live embryos, resulting mainly from an increase in preimplantation loss was observed in the females mated with the nickel-treated males.
34 Demopoulos, N., and A. Kappas, Department of Genetics, University of Patras, Patras, and Biology Department, Nuclear Research Center 'Democritus', Athens (Greece) The use of Aspergillus nidulans as a test system for extranuclear mutations induced by environmental chemicals
Amongst the filamentous fungi, extranuclear mitochondrial mutants have been isolated in Neurospora crassa, Aspergillus nidulans and others. Regarding Aspergillus it is most likely that extranuclear mutations affecting mitochondrial function are located in mitochondrial DNA (Turner, G., and R.T. Rowlands, in: Genetics and Physiology of Aspergillus, Academic Press, New York, 1977, pp. 319-337). A. nidulans has been screened for sensitivity to a large number of inhibitors of mitochondrial function amongst which oligomycin was found to be very effective.
181 We looked for oligomycin-resistant mutants in the strain 237 (y A 2 pyro A 4 cnx C 3) of A. nidulans by treating conidial suspensions with the mutagen N T G , the fungicide captan and the antitumor antibiotic ble.omycin. Further, by forming heterokaryons between the resistant mutants and sensitive properly marked strains, we determined whether the oligomycin resistance was due to nuclear and/or mitochondrial DNA mutations. By analysing 12, 3 and 5 resistant mutants induced by NTG, captan and bleomycin respectively, we found that NTG induced both nuclear and extranuclear mutations (9:3) but captan and bleomycin induced only nuclear mutations in the strain studied. 35 Della Morte, R., G. Vricella, N. Staiano and F. De Lorenzo, 2a Cattedra di Chimica Biologica, 2a Facolth di Medicina e Chirurgia, Universith di Napoli, Via S. Pansini, 5, 80131, Naples (Italy) Effects of microsomal enzyme inducers on the in vivo activation of cyclophosphamide to mutagenic metabolites Cyclophosphamide is used extensively as an antineoplastic agent for the treatment of various cancers and as immunosuppressive agent. Active metabolites of cyclophosphamide rather than the parent compound have alkylating activity and cause cytotoxicity, oncogenic transformation and chromosomal aberrations. The activation of cyclophosphamide occurs primarily in the liver and is mediated by a cytochrome P-450 mono-oxygenase system. It has been reported that the production of mutagenic metabolites of cyclophosphamide in vitro by male rat liver is enhanced by the phenobarbital-induced cytochrome P-450 rather than by the polycyclic aromatic hydrocarbon-induced cytochrome P-448. We are studying the characteristics of the in vivo activation of cyclophosphamide to urinary metabolites that are mutagenic to Salmonella typhimurium TA1535. The 24-h urines from rats treated with cyclophosphamide show a 100-fold increase in revertant rate over the control as measured by the Ames Salmonella test system. We are evaluating the effect of various inducers of cytochrome(s) P-450 as well as inhibitors upon the mutagenicity of urinary metabolites of cyclophosphamide. 36 De Marco, A., and S. Polani, Centro di Genetica Evoluzionistica del CNR, c / o Istituto di Genetica, Universith, Rome (Italy) Analysis of chromosome aberrations induced by cyclophosphamide, mitomycin C and bleomycin in somatic cells of Drosophila melanogaster We have analyzed the chromosome aberrations induced in the nerve ganglia of third instar larvae of Drosophila melanogaster by some compounds having a different capacity to induce sex-linked recessive lethals. The effect of treatment was examined
for malathion (8ppm), 0.026 mg/kg for methyl parathion (0.15 ppm), and 0.09 mg/kg for trichlorfon (0.5 ppm). At the end of the treatment, cytogenetic effects were analysed in bone-marrow cells, spermatogonia, and diakinesis, and genetic effects were investigated in the dominant lethal mutation test. In the 3 cytogenetic systems, the frequency of fragments, exchanges and gaps was not found to be enhanced over the control level. In the dominant lethal mutation test, the results obtained for the frequency of pre-implantation losses, postimplantation deaths, and live embryos per female were within the control limits.
33 Deknudt, Gh., Laboratory of Genetics, Department of Radiobiology, S.C.K.-C.E.N., B-2400 Mol (Belgium) In vivo study of the mutagenicity of heavy metals in mammals
The dominant lethal test has been performed over a period of 5 weeks to study in BALB/c mice the mutagenic activity of 2 chromium compounds, potassium dichromate (K2Cr2OT) and calcium chromate (CaCrO4) and 2 nickel compounds, nickel nitrate (Ni(NO3) 2) and nickel chloride (NiC12). The doses were chosen on the basis of a preliminary experiment and correspond roughly to one half of the LDs000): K2CrO 7, 20 mg/kg; Ni(NO3) 2, 56 mg/kg; NiC12, 25 mg/kg. Due to the low solubility of the compound, an 8-fold lower concentration of CaCrO4 (40 mg/kg) was used. The chromium and nickel compounds produced a significant reduction in the rate of pregnancies. Furthermore, a lower incidence of live embryos, resulting mainly from an increase in preimplantation loss was observed in the females mated with the nickel-treated males.
34 Demopoulos, N., and A. Kappas, Department of Genetics, University of Patras, Patras, and Biology Department, Nuclear Research Center 'Democritus', Athens (Greece) The use of Aspergillus nidulans as a test system for extranuclear mutations induced by environmental chemicals
Amongst the filamentous fungi, extranuclear mitochondrial mutants have been isolated in Neurospora crassa, Aspergillus nidulans and others. Regarding Aspergillus it is most likely that extranuclear mutations affecting mitochondrial function are located in mitochondrial DNA (Turner, G., and R.T. Rowlands, in: Genetics and Physiology of Aspergillus, Academic Press, New York, 1977, pp. 319-337). A. nidulans has been screened for sensitivity to a large number of inhibitors of mitochondrial function amongst which oligomycin was found to be very effective.
181 We looked for oligomycin-resistant mutants in the strain 237 (y A 2 pyro A 4 cnx C 3) of A. nidulans by treating conidial suspensions with the mutagen N T G , the fungicide captan and the antitumor antibiotic ble.omycin. Further, by forming heterokaryons between the resistant mutants and sensitive properly marked strains, we determined whether the oligomycin resistance was due to nuclear and/or mitochondrial DNA mutations. By analysing 12, 3 and 5 resistant mutants induced by NTG, captan and bleomycin respectively, we found that NTG induced both nuclear and extranuclear mutations (9:3) but captan and bleomycin induced only nuclear mutations in the strain studied. 35 Della Morte, R., G. Vricella, N. Staiano and F. De Lorenzo, 2a Cattedra di Chimica Biologica, 2a Facolth di Medicina e Chirurgia, Universith di Napoli, Via S. Pansini, 5, 80131, Naples (Italy) Effects of microsomal enzyme inducers on the in vivo activation of cyclophosphamide to mutagenic metabolites Cyclophosphamide is used extensively as an antineoplastic agent for the treatment of various cancers and as immunosuppressive agent. Active metabolites of cyclophosphamide rather than the parent compound have alkylating activity and cause cytotoxicity, oncogenic transformation and chromosomal aberrations. The activation of cyclophosphamide occurs primarily in the liver and is mediated by a cytochrome P-450 mono-oxygenase system. It has been reported that the production of mutagenic metabolites of cyclophosphamide in vitro by male rat liver is enhanced by the phenobarbital-induced cytochrome P-450 rather than by the polycyclic aromatic hydrocarbon-induced cytochrome P-448. We are studying the characteristics of the in vivo activation of cyclophosphamide to urinary metabolites that are mutagenic to Salmonella typhimurium TA1535. The 24-h urines from rats treated with cyclophosphamide show a 100-fold increase in revertant rate over the control as measured by the Ames Salmonella test system. We are evaluating the effect of various inducers of cytochrome(s) P-450 as well as inhibitors upon the mutagenicity of urinary metabolites of cyclophosphamide. 36 De Marco, A., and S. Polani, Centro di Genetica Evoluzionistica del CNR, c / o Istituto di Genetica, Universith, Rome (Italy) Analysis of chromosome aberrations induced by cyclophosphamide, mitomycin C and bleomycin in somatic cells of Drosophila melanogaster We have analyzed the chromosome aberrations induced in the nerve ganglia of third instar larvae of Drosophila melanogaster by some compounds having a different capacity to induce sex-linked recessive lethals. The effect of treatment was examined