- Email: [email protected]
Phencyclidine and environmental teratogen
348
Ist INTERNATIONALCONFERENCE, ASILOMAR
7 NAKAI, SAYAKA, AND ISAMU MACHIDA,Division of Genetics, National Institute of Radiological Sciences, Anagawa, Chiba (Japan).
Genetic effect of organic mercury on yeast This report is concerned with the effect of methyl mercury chloride on the yeast Saccharomyces cerevisiae, which is a useful and convenient organism for the assay of alterations such as mutation, conversion, or recombination. On survivals, an X-ray-sensitive mutant, XSI, is significantly more susceptible than wild type is. The dose reduction factor was about 2 instead of 8 by X-rays. But an UV-sensitive mutant, UVSI, is not obvious. Note that in wild-type diploid cells, the sensitivity to organic mercury depends on the growth phase of this organism, that is, the cells in the early log-phase is very sensitive and its dose-increment factor is about 20 when compared with that in the stational phase. This information suggests that the stage of nuclear division is responsible for the critical time of lethal effect of mercury. Mutagenic action of organic mercury could be observed in the induction of cytoplasmic petite mutation. However, nuclear gene mutation could not be induced when measured the reversion of lysi-i, a nonsense mutant of ochre type, and of hisI-I, a frameshift mutant, respectively. Induced gene conversion between leuI-I and leuI-I2 and mitotic recombination between centromere and cyc2 on the chromosome V I I were not observed. However, induction of mitotic non-disjunction which was measured by cyc2linked markers on the chromosome V I I seemed to be slightly increased.
8 WALKER, FRANK A., AND JILL ANN SEIG, Children's Psychiatric Research Institute, London, Ont. (Canada), and Cytogenetics Laboratory, Milwaukee Children's Hospital, Milwaukee, Wis. (U.S.A.).
Phencyclidine and environmental teratogen In the past 5 years two clusters of anomalies have occurred in infants born to parents involved in the drug culture. One group involved limb reduction defects and was seen as a clustering effect in time and space at several centres across North America. A second group involved an increased occurrence of live born triploid infants similarly. Retrospective investigation suggested that the parents had ingested phencyclidine containing street drugs during the early first trimester in the group with limb reduction defects and prior to conception during the time of spermatogenesis in the male consort among the parents who had produced triploid infants. Prospective chromosome studies on the parents showed an increased occurrence of additional Flike chromosome in those individuals who had been using drugs which had contained phencyclidine. The occurrence of the chromosome abnormality appeared to decrease with time when successive chromosome studies were done. Individuals who had utilized the same batch of street drugs did not necessarily show the same chromosome abnormality. It is suggested that phencyclidine m a y undergo degradation similar to that of the cyclamates to produce a metabolic similar to cycohexylamine which could
THE AMERICAN ENVIRONMENTAL MUTAGEN SOCIETY
349
produce the observed abnormalities. This would suggest that a genetically determined alternate metabolic pathway may convert an apparently harmless psychotrophic drug into potential teratogenic metabolite.
9 WOLFF, SHELDON, Laboratory of Radiobiology, University of California, San Francisco, Calif. (U.S.A.).
Absence of repair replication in Vicia faba after treatment with chemical mutagens Unscheduled DNA synthesis and repair replication represent excision repair and are thought to be universal repair processes. Nevertheless, they do not occur in Viciafaba root tips after X-irradiation. Because repair replication occurs more readily in mammalian cells after UV light than X-rays, attempts were made to see if this type of repair could be found in Vicia after UV-like lesions were induced. UV light itself does not penetrate into the roots very readily, so 4NQO which induces "UV-like lesions" in bacteria was used. Concomitantly, experiments were also carried out with MNNG which induces "X-ray-like lesions". Growing roots of Vicia were treated with BrUdR for 3 h so that all newly replicated DNA would be heavy hybrid molecules. The roots were then treated with 5 '1o-4 M MNNG or 4NQO for i h which was then followed by treatment with EaHIBrUdR for 4 h. Cesium chloride and cesium sulphate density gradient analyses of both double- and single-stranded DNA showed no incorpoiation of iaH]BrUdR into parental weight molecules, i.e., no repair replication was found. This finding indicates that repair replication can be absent from normal organisms. Since chromosome breaks undergo repair in Vicia, the data also carry the implication that such chromosome repair is independent of repair replication. Work performed under the auspices of the U.S. Atomic Energy Commission. Abbreviations: BrUdR, 5-bromodeoxyuridine; MNNG, N-methyl-N'-nitro-N-nitrosoguanidine; 4NQO, 4-nitroquinoline- I-oxide.
10 RODERICK, THOMAS H., The Jackson Laboratory, Bar Harbor, Me. (U.S.A.).
Using an inversion for assessing recessive mutations in mice Inversion In(I)IRk on Chromosome I includes loci Sp (Splotch) and In (leaden) and with them provides a system for assessing induced recessive lethals, detrimentals and visibles in the mouse. The induction of a recessive is inferred from an absence, reduction, or peculiarity in the non-splotch class of animals in generation III. Two isozyme loci, Id-z (Isocitrate dehydrogenase-i) and Dip-z (Dipeptidase-i), are included in the inversion making it further useful in assessing point mutations simultaneously at those loci. The frequency of dominant visibles, semisterility, and sterility can also be studied in the first generation. This inversion effectively eliminates
Ist INTERNATIONALCONFERENCE, ASILOMAR
7 NAKAI, SAYAKA, AND ISAMU MACHIDA,Division of Genetics, National Institute of Radiological Sciences, Anagawa, Chiba (Japan).
Genetic effect of organic mercury on yeast This report is concerned with the effect of methyl mercury chloride on the yeast Saccharomyces cerevisiae, which is a useful and convenient organism for the assay of alterations such as mutation, conversion, or recombination. On survivals, an X-ray-sensitive mutant, XSI, is significantly more susceptible than wild type is. The dose reduction factor was about 2 instead of 8 by X-rays. But an UV-sensitive mutant, UVSI, is not obvious. Note that in wild-type diploid cells, the sensitivity to organic mercury depends on the growth phase of this organism, that is, the cells in the early log-phase is very sensitive and its dose-increment factor is about 20 when compared with that in the stational phase. This information suggests that the stage of nuclear division is responsible for the critical time of lethal effect of mercury. Mutagenic action of organic mercury could be observed in the induction of cytoplasmic petite mutation. However, nuclear gene mutation could not be induced when measured the reversion of lysi-i, a nonsense mutant of ochre type, and of hisI-I, a frameshift mutant, respectively. Induced gene conversion between leuI-I and leuI-I2 and mitotic recombination between centromere and cyc2 on the chromosome V I I were not observed. However, induction of mitotic non-disjunction which was measured by cyc2linked markers on the chromosome V I I seemed to be slightly increased.
8 WALKER, FRANK A., AND JILL ANN SEIG, Children's Psychiatric Research Institute, London, Ont. (Canada), and Cytogenetics Laboratory, Milwaukee Children's Hospital, Milwaukee, Wis. (U.S.A.).
Phencyclidine and environmental teratogen In the past 5 years two clusters of anomalies have occurred in infants born to parents involved in the drug culture. One group involved limb reduction defects and was seen as a clustering effect in time and space at several centres across North America. A second group involved an increased occurrence of live born triploid infants similarly. Retrospective investigation suggested that the parents had ingested phencyclidine containing street drugs during the early first trimester in the group with limb reduction defects and prior to conception during the time of spermatogenesis in the male consort among the parents who had produced triploid infants. Prospective chromosome studies on the parents showed an increased occurrence of additional Flike chromosome in those individuals who had been using drugs which had contained phencyclidine. The occurrence of the chromosome abnormality appeared to decrease with time when successive chromosome studies were done. Individuals who had utilized the same batch of street drugs did not necessarily show the same chromosome abnormality. It is suggested that phencyclidine m a y undergo degradation similar to that of the cyclamates to produce a metabolic similar to cycohexylamine which could
THE AMERICAN ENVIRONMENTAL MUTAGEN SOCIETY
349
produce the observed abnormalities. This would suggest that a genetically determined alternate metabolic pathway may convert an apparently harmless psychotrophic drug into potential teratogenic metabolite.
9 WOLFF, SHELDON, Laboratory of Radiobiology, University of California, San Francisco, Calif. (U.S.A.).
Absence of repair replication in Vicia faba after treatment with chemical mutagens Unscheduled DNA synthesis and repair replication represent excision repair and are thought to be universal repair processes. Nevertheless, they do not occur in Viciafaba root tips after X-irradiation. Because repair replication occurs more readily in mammalian cells after UV light than X-rays, attempts were made to see if this type of repair could be found in Vicia after UV-like lesions were induced. UV light itself does not penetrate into the roots very readily, so 4NQO which induces "UV-like lesions" in bacteria was used. Concomitantly, experiments were also carried out with MNNG which induces "X-ray-like lesions". Growing roots of Vicia were treated with BrUdR for 3 h so that all newly replicated DNA would be heavy hybrid molecules. The roots were then treated with 5 '1o-4 M MNNG or 4NQO for i h which was then followed by treatment with EaHIBrUdR for 4 h. Cesium chloride and cesium sulphate density gradient analyses of both double- and single-stranded DNA showed no incorpoiation of iaH]BrUdR into parental weight molecules, i.e., no repair replication was found. This finding indicates that repair replication can be absent from normal organisms. Since chromosome breaks undergo repair in Vicia, the data also carry the implication that such chromosome repair is independent of repair replication. Work performed under the auspices of the U.S. Atomic Energy Commission. Abbreviations: BrUdR, 5-bromodeoxyuridine; MNNG, N-methyl-N'-nitro-N-nitrosoguanidine; 4NQO, 4-nitroquinoline- I-oxide.
10 RODERICK, THOMAS H., The Jackson Laboratory, Bar Harbor, Me. (U.S.A.).
Using an inversion for assessing recessive mutations in mice Inversion In(I)IRk on Chromosome I includes loci Sp (Splotch) and In (leaden) and with them provides a system for assessing induced recessive lethals, detrimentals and visibles in the mouse. The induction of a recessive is inferred from an absence, reduction, or peculiarity in the non-splotch class of animals in generation III. Two isozyme loci, Id-z (Isocitrate dehydrogenase-i) and Dip-z (Dipeptidase-i), are included in the inversion making it further useful in assessing point mutations simultaneously at those loci. The frequency of dominant visibles, semisterility, and sterility can also be studied in the first generation. This inversion effectively eliminates