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The genotoxic potential of bases and nucleosides
165 4 A1-Mossawi, M.A.J., A.A. Salem, M. Salama a n d A. Anani, Kuwait Institute for Scientific Research, Post Box No. 24885, Safat (Kuwait) The microbial mutagenicity and toxicity of newly synthesized heterocyclic N-oxides
Newly synthesized heterocyclic N-oxides were tested for their mutagenicity using the Ames test. DX1 was potentially mutagenic in Salmonella typhimurium TA100 and TA98 with and without $9 mix. WO-25 and WO-20, which are structurally related to DX 1 did not show any genetic change in the strains used. The antibiotic activity of these chemicals was also tested using gram-negative and gram-positive bacteria. The mutagenic chemical DX1 had more killing effect in gram-positive bacteria than WO-25 and WO-20.
5 Altukhov, Yu.P., Institute of General Genetics, Moscow (U.S.S.R.) Mutation rate in man under selection pressure against rare protein variants
The reliable estimate of gene mutation rate in man is of primary importance in condi~ons of environmental pollution. Some approaches to this problem based on the technique of blood protein electrophoresis have been recently proposed in the U.S.S.R. and the U.S.A. According to Neel (1980), the mutation rate of the genes in question cannot be higher than 0.6 X 10-5 per locus per generation. This estimate implies that de novo mutations that change protein structure are selectively neutral. According to our estimations the mutation rate of protein loci in humans is higher by an order of magnitude since de novo mutations are eliminated at the early stages of development by stabilizing selection (Dubinin and Altukhov, 1979). The significance of this fact for human genetics, medicine and organisation of population monitoring is discussed.
6 Anderson, D., C.R. Richardson and P.J. Davies I, ICI Limited, Central Toxicology Laboratory, Alderley Park, Near Macclesfield, Cheshire SK10 4TJ, and 1Department of Genetics, University College of Swansea, Singleton Park, Swansea, Glamorganshire, Wales SA2 8PP (Great Britain) The genotoxic potential of bases and nucleosides
This study was conducted to determine if naturally occurring cell constituents could themselves cause mutation. All the bases and their corresponding nucleosides have been shown to produce chromosome damage in P388 mouse lymphoma and Chinese hamster ovary cells in culture. In addition thymidine has produced an
166
increase in V79 cells resistant to 8-azaguanine and ouabain. Such damage probably arises as a result of imbalanced DNA precursor pools. Thus mutagenic events may arise by mechanisms unrelated to direct alterations of DNA.
7 Arany, J., and G. Jenar-Du Buisson, Institut d'Hygi6ne et d'Epid6miologie, Brussels (Belgium) Sperm abnormalities and prenatal losses in the mouse
Prenatal losses, sperm abnormalities (AS) and 3-methylcholanthrene-induced aryl hydrocarbon hydroxylase (AHH) activity were compared for 4 strains of mice (BALB/c, C57B1/6, CBA, AKR). There is a striking correlation (r) between post-implantation losses, AS and AHH values. It seems therefore that the postimplantation losses could be due to sperm abnormalities. Furthermore, strain differences could be explained by the characteristics of the Ah locus.
8 Arany, J., G. Jenar-Du Buisson and J. Henrotte, Institut d'Hygi~ne et d'Epid~miologie, Brussels (Belgium) Influence of the number of bacteria used in the Salmonella/microsome test
We examined the influence of the number of bacteria used in the Salmonella/microsome test. We performed the test with different dilutions of the bacterial culture which has been prewashed or not with minimal medium to eliminate the histidine content. The mutagen used was benzo[a]pyrene. The results seem to show that: (1) In prewashed cultures the number of bacteria has only a slight influence on the number of spontaneous revertants whereas the histidine content of an unwashed cell suspension is much more determinant. Interlaboratory differences in the number of spontaneous revertants could be due to the remaining histidine left in the culture medium after overnight culture of the cells. (2) The induction rate of revertants for low concentrations of the mutagen is fairly independent of the number of bacteria but for higher concentrations there is a decrease of mutagenicity with increased dilutions of the bacteria.
9 Arlett, C.F., J. Cole, B.C. Broughton and B.A. Bridges, MRC Cell Mutation Unit and Sussex Centre for Medical Research, University of Sussex, Falmer, Brighton (Great Britain) Mutagenic effects of 1,8-dinitropyrene on cultured human and mouse cells
Newly synthesized heterocyclic N-oxides were tested for their mutagenicity using the Ames test. DX1 was potentially mutagenic in Salmonella typhimurium TA100 and TA98 with and without $9 mix. WO-25 and WO-20, which are structurally related to DX 1 did not show any genetic change in the strains used. The antibiotic activity of these chemicals was also tested using gram-negative and gram-positive bacteria. The mutagenic chemical DX1 had more killing effect in gram-positive bacteria than WO-25 and WO-20.
5 Altukhov, Yu.P., Institute of General Genetics, Moscow (U.S.S.R.) Mutation rate in man under selection pressure against rare protein variants
The reliable estimate of gene mutation rate in man is of primary importance in condi~ons of environmental pollution. Some approaches to this problem based on the technique of blood protein electrophoresis have been recently proposed in the U.S.S.R. and the U.S.A. According to Neel (1980), the mutation rate of the genes in question cannot be higher than 0.6 X 10-5 per locus per generation. This estimate implies that de novo mutations that change protein structure are selectively neutral. According to our estimations the mutation rate of protein loci in humans is higher by an order of magnitude since de novo mutations are eliminated at the early stages of development by stabilizing selection (Dubinin and Altukhov, 1979). The significance of this fact for human genetics, medicine and organisation of population monitoring is discussed.
6 Anderson, D., C.R. Richardson and P.J. Davies I, ICI Limited, Central Toxicology Laboratory, Alderley Park, Near Macclesfield, Cheshire SK10 4TJ, and 1Department of Genetics, University College of Swansea, Singleton Park, Swansea, Glamorganshire, Wales SA2 8PP (Great Britain) The genotoxic potential of bases and nucleosides
This study was conducted to determine if naturally occurring cell constituents could themselves cause mutation. All the bases and their corresponding nucleosides have been shown to produce chromosome damage in P388 mouse lymphoma and Chinese hamster ovary cells in culture. In addition thymidine has produced an
166
increase in V79 cells resistant to 8-azaguanine and ouabain. Such damage probably arises as a result of imbalanced DNA precursor pools. Thus mutagenic events may arise by mechanisms unrelated to direct alterations of DNA.
7 Arany, J., and G. Jenar-Du Buisson, Institut d'Hygi6ne et d'Epid6miologie, Brussels (Belgium) Sperm abnormalities and prenatal losses in the mouse
Prenatal losses, sperm abnormalities (AS) and 3-methylcholanthrene-induced aryl hydrocarbon hydroxylase (AHH) activity were compared for 4 strains of mice (BALB/c, C57B1/6, CBA, AKR). There is a striking correlation (r) between post-implantation losses, AS and AHH values. It seems therefore that the postimplantation losses could be due to sperm abnormalities. Furthermore, strain differences could be explained by the characteristics of the Ah locus.
8 Arany, J., G. Jenar-Du Buisson and J. Henrotte, Institut d'Hygi~ne et d'Epid~miologie, Brussels (Belgium) Influence of the number of bacteria used in the Salmonella/microsome test
We examined the influence of the number of bacteria used in the Salmonella/microsome test. We performed the test with different dilutions of the bacterial culture which has been prewashed or not with minimal medium to eliminate the histidine content. The mutagen used was benzo[a]pyrene. The results seem to show that: (1) In prewashed cultures the number of bacteria has only a slight influence on the number of spontaneous revertants whereas the histidine content of an unwashed cell suspension is much more determinant. Interlaboratory differences in the number of spontaneous revertants could be due to the remaining histidine left in the culture medium after overnight culture of the cells. (2) The induction rate of revertants for low concentrations of the mutagen is fairly independent of the number of bacteria but for higher concentrations there is a decrease of mutagenicity with increased dilutions of the bacteria.
9 Arlett, C.F., J. Cole, B.C. Broughton and B.A. Bridges, MRC Cell Mutation Unit and Sussex Centre for Medical Research, University of Sussex, Falmer, Brighton (Great Britain) Mutagenic effects of 1,8-dinitropyrene on cultured human and mouse cells