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Biochemical Approaches to Monitoring Human Populations for Germinal Mutation Rates: II. Enzyme Deficiency Variants as a Component of the Estimated Genetic Risk

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Utilization of Mammalian Specific Locus Studies in Hazard Evaluation and Estimation of Genetic Risk

Part of the book series: Environmental Science Research ((ESRH,volume 28))

Abstract

The ultimate function of toxicology screening systems is to provide an accurate estimate of the human health risk associated with exposure to potentially hazardous agents. A number of test systems, with varying capabilities, have been developed and it has been proposed that combinations of several of these systems be utilized in a tier approach to estimating risk. The shortcomings of the various components of the tier system, including differences in metabolic pathways, target tissue specificity, cell replication, etc., have been discussed [1]. An additional problem is the lack of relevant data from human populations which may be used as a reference for extrapolation. That is, it is difficult to estimate human health risk utilizing data obtained in test systems in the absence of at least some data from a limited number of studies relating the nature and extent of exposure, the frequency of events induced and the associated increase in health costs in a human population. The absence of a data base is most apparent for germinal mutations, where except for genetic damage involving structural or numerical chromosomal abberations [2–4], the data on the frequency of possible mutagenic events, either spontaneous or induced, are very limited. Most previous estimates of the frequency of mutational events in human populations have utilized either the population characteristic or sentinel phenotype approach [5–7]. Recently, electrophoretic techniques have been developed which can be used to obtain data relevant to the estimation of both the background and induced mutation rate in human populations [8–10]. The current status of these electrophoretic methodologies is described by Neel et al., in a companion paper in this symposium [11].

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References

  1. Committee 17, Environmental mutagenic hazards, Science, 187: 503–514 (1975).

    Article  Google Scholar 

  2. D. Z. Warburton, J. Stein, J. Kline, and M. Susser, in: “Human Embryonic and Fetal Death,” I. H. Porter and E. B. Hook, eds., pp. 261–287, Academic Press, New York (1980).

    Google Scholar 

  3. P. A. Jacobs, Mutation rates of structural chromosome rearrangements in man, Am. J. Hum. Genet., 33:44–54 (1981).

    Google Scholar 

  4. E. B. Hook, Contribution of chromosome abnormalities to human morbidity and mortality and some comments upon surveillance of chromosome mutation rates, Prog. Mutat. Res., 3:9–38 (1982).

    Google Scholar 

  5. F. Vogel, in: “Chemical Mutagenesis in Mammals and Man,” F. Vogel and G. Rohrborn, eds., pp. 16–68, Springer-Verlag, New York (1970).

    Google Scholar 

  6. F. Vogel and R. Rathenberg, Spontaneous mutations in man, Advan. Hum. Genet., 5:223–317 (1975).

    Google Scholar 

  7. J. V. Neel, The detection of increased mutation rates in human populations, Persp. Biol. Med., 522–537 (1971).

    Google Scholar 

  8. J. V. Neel, H. W. Mohrenweiser, and M. M. Meisler, Rate of spontaneous mutation at human loci encoding protein structure, Proc. Natl. Acad. Sci. USA, 77:6037–6041 (1980).

    Article  ADS  Google Scholar 

  9. J. V. Neel, C. Satoh, H. B. Hamilton, M. Otake, K. Goriki, T. Kagoeka, M. Fijita, S. Neriishi, and J. Asakawa, A search for mutations affecting protein structure in children of atomic bomb survivors: preliminary report, Proc. Natl. Acad. Sci. USA, 77:4221–4225 (1980).

    Article  ADS  Google Scholar 

  10. F. Vogel and K. Altland, Utilization of material from PKU-screening programs for mutation screening, Prog. Mutat. Res., 3:143–157 (1982).

    Google Scholar 

  11. J. V. Neel, H. Mohrenweiser, S. Hanash, B. Rosenblum, S. Sternberg, K. H. Wurzinger, E. Rothman, C. Satoh, K. Goriki, T. Krasteff, M. Long, M. Skolnick, and R. Krezesicki, Biochemical approaches to monitoring human populations for germinal mutation rates: I. Electrophoresis, (current proceedings).

    Google Scholar 

  12. H. Friedmann and S. M. Rapoport, in: “Cellular and Molecular Biology of Erythrocytes,” H. Yoshikawa, ed., pp. 181–259, University Park Press, Baltimore (1974).

    Google Scholar 

  13. A. J. Grimes and G. C. de Gruchy, in: “Blood and It’s Disorders,” R. M. Hardestry and D. J. Weatherald, eds., pp. 473–525, Blackwell, London (1974).

    Google Scholar 

  14. J. B. Stanbury, J. B. Wyngaarden, and D. S. Fredrickson, in: “The Metabolic Basis of Inherited Diseases,” J. B. Stanbury, J. B. Wyngaarder, and D. S. Fredrickson, eds., pp. 2–31, Mraw Hill, New York (1978).

    Google Scholar 

  15. W. N. Valentine, Deficiencies associated with Embden-Meyerhof pathway and other metabolic pathways, Semin. in Hematol., 8: 348–366 (1971).

    Google Scholar 

  16. E. Beutler, Red cell enzyme defects as nondiseases and diseases, Blood, 54:1–7 (1979).

    Google Scholar 

  17. A. Kahn, J. C. Kaplan, and J. C. Dreyfus, Advances in hereditary red cell anomalies, Hum. Genet., 51:1–27 (1979).

    Article  Google Scholar 

  18. K. O. Raivio and J. E. Seegmiller, Genetic diseases of metabolism, Ann. Rev. Biochem., 41:543–576 (1972).

    Article  Google Scholar 

  19. S. Miwa, H. Fujii, S. Takegawa, T. Nakatsiui, K. Yamato, Y. Ishida, and N. Ninomiya, Seven pyruvate kinase variants characterized by the ICSH recommended methods, Brit. J. Haemat., 45, 576–583 (1980).

    Article  Google Scholar 

  20. J.-L. Vives-Corrons, H. Rubinson-Skala, M. Mateo, J. Estella, E. Feliu, and J.-C. Dreyfus, Triosephosphate isomerase deficiency with hemolytic anemia and severe neuromuscular disease. Familial and biochemical studies of a case in Spain, Hum. Genet., 42:171–180 (1978).

    Article  Google Scholar 

  21. A. G. L. Whitelaw, P. A. Rogers, D. A. Hopkinson, H. Gordon, P. M. Emerson, J. H. Darley, C. Reed, and M. A. Crawford, Congenital haemolytic anaemia resulting from glucosephosphate isomeriase deficiency: genetics, clinical picture and prenatal diagnosis, J. Med. Genet., 16:189–196 (1979).

    Article  Google Scholar 

  22. H. W. Mohrenweiser and J. Novotny, An enzymatically inactive variant of human lactate dehydrogenase-LDH B GUA-1: Study of subunit interaction, Biochem. Biophys. Acta, 702:90–98 (1982).

    Article  Google Scholar 

  23. H. W. Mohrenweiser, Frequency of enzyme deficiency variants in erythrocytes of newborn infants, Proc. Natl. Acad. Sci. USA, 78:5046–5050 (1981).

    Article  ADS  Google Scholar 

  24. H. W. Mohrenweiser, Frequency of rare enemy deficiency variants: Search for mutational events with human health implications, Prog. Mutat. Res., 3:159–162 (1982).

    Google Scholar 

  25. A. Morelli, U. Benatti, G. F. Gaetami, and A. DeFlora, Biochemical mechanisms of glucose 6-phosphate dehydrogenase deficiency, Proc. Natl. Acad. Sci. USA, 75:1979–1983 (1978).

    Article  ADS  Google Scholar 

  26. J. V. Neel, H. W. Mohrenweiser, C. Satoh, and H. B. Hamilton, in: “Genetic Damage in Man Caused by Environmental Agents,” K. Borg, ed., pp. 29–47, Academic Press, New York (1979).

    Google Scholar 

  27. S. Fielek and H. W. Mohrenweiser, Erythrocyte enzyme deficiencies assessed with a miniature centrifugal analyzer, Clin. Chem., 205:384–388 (1979).

    Google Scholar 

  28. H. Mohrenweiser and S. Fielek, Elevated frequency of carriers for triosephosphate isomerase deficiency in newborn infants, Ped. Res., 16:960–963 (1982).

    Article  Google Scholar 

  29. C. Satoh, A. A. Awa, J. V. Neel, W. J. Schull, H. Kato, H. B. Hamilton, M. Otake, and K. Goriki, Genetic effects of atomic bombs, Proc. Int. Cong. Human Genet., in press (1982).

    Google Scholar 

  30. S. W. Eber, B. H. Belohradsky, and W. K. G. Krietsch, A case for triosephosphate isomerase testing in congential nonspherocytic hemolytic anemia, J. Pediat., in press (1983).

    Google Scholar 

  31. S. W. Eber, M. Dunnwald, B. H. Belshradsky, F. Bidlingmaier, H. Schievelbein, H. M. Weinman, and W. K. G. Krietsch, Hereditary deficiency of triosephosphate isomerase in four unrelated families, Eur. J. Clin. Investig., 9:195–202 (1979).

    Article  Google Scholar 

  32. W. K. G. Krietsch, H. Krietsch, W. Kaiser, M. Dunnwald, G. Kuntz, I. Duhm, and T. Bucher, Hereditary deficiency of phosphoglycerate kinase: a rare variant in erythrocytes and leucocytes not associated with haemolytic anaemia, Eur. J. Clin. Investig., 7:427–425 (1977).

    Article  Google Scholar 

  33. H. Harris, D. A. Hopkinson, and E. B. Robson, The incidence of rare alleles determining electrophoretic variants: data on 43 enzyme loci in man, Ann. Hum. Genet. (Lond.), 37:237–253 (1974).

    Article  Google Scholar 

  34. P. T. Wade-Cohen, G. S. Omenn, A. G. Motulsky, S. H. Chen, and E. R. Giblett, Restricted variation in the glycolytic enzymes of human brain and erythrocytes, Nature, 241:229–233 (1973).

    Article  Google Scholar 

  35. H. W. Mohrenweiser and J. V. Neel, Frequency of thermostability variants: Estimation of total “rare” variant frequency in human populations, Proc. Natl. Acad. Sci. USA, 78:5729–5783 (1981).

    Article  ADS  Google Scholar 

  36. C. H. Langley, R. A. Voelker, A. J. Leigh-Brown, S. Ohnishi, B. Dickson, and E. Montgomery, Null allele frequency at allozyme loci in natural populations of Drosophila melanogaster, Genetics, 99:151–156 (1981).

    Google Scholar 

  37. R. A. Voelker, C. H. Langley, A. J. Leigh-Brown, S. Ohnishi, B. Dickson, E. Montgomery, and S. C. Smith, Enzyme null alleles in natural populations of Drosophila melanogaster: Frequencies in a North Carolina population, Proc. Natl. Acad. Sci. USA, 77:1091–1095 (1980).

    Article  ADS  Google Scholar 

  38. T. Mukai and C. C. Cockerham, Spontaneous mutation rates at enzyme loci in Drosophilia melanogaster, Proc. Natl. Acad. Sci. USA, 74:2514–2517 (1977).

    Article  ADS  Google Scholar 

  39. R. A. Voelker, H. E. Scheffer, and T. Mukai, Spontaneous allozyme mutations in Drosophilia melanogaster: Rate of occurrence and nature of the mutants, Genetics, 94:961–968 (1980).

    Google Scholar 

  40. W. Prestsch and D. Charles, in: “Electrophoresis 1979: Adv. Methods, Biochemical Clinical Appl.” B. J. Radola, ed., pp. 817–824, DeGruyter, Berlin (1980).

    Google Scholar 

  41. F. M. Johnson and S. E. Lewis, Electrophoretically detected germinal mutations induced in the mouse by ethylnitrosourea, Proc. Natl. Acad. Sci. USA, 78:3138–3141 (1981).

    Article  ADS  Google Scholar 

  42. W. L. Russell and E. M. Kelly, Specific locus mutation frequencies in mouse stem-cell spermatogonia at very low radiation dose rates, Proc. Natl. Acad. Sci. USA, 79:539–542 (1982).

    Article  ADS  Google Scholar 

  43. A. G. Searle, Mutation induction in mice, Adv. Radiat. Biol., 4:131–207 (1974).

    Google Scholar 

  44. L. B. Russell, Definition of functional units in a small chromosomal segment of the mouse and its use in interpreting the nature of radiation-induced mutations, Mutat. Res., 11:107–123 (1971).

    Article  Google Scholar 

  45. L. B. Russell, W. L. Russell, and E. M. Kelly, Analysis of the albino-locus region of the mouse, Genetics, 91:127–139 (1979).

    Google Scholar 

  46. R. R. Racine, C. H. Langley, and R. A. Voelker, Enzyme mutants induced by low-dose-rate y-irradiation in Drosophila: Frequency and characterization, Environ. Mutagen., 2:167–177 (1980).

    Article  Google Scholar 

  47. L. B. Russell, W. L. Russell, R. A. Popp, C. Vaughan, and K. B. Jacobson, Radiation-induced mutations at mouse hemoglobin loci, Proc. Natl. Acad. Sci. USA, 73:2843–2846 (1976).

    Article  ADS  Google Scholar 

  48. H. V. Mailing, and L. R. Valcovic, Biochemical specific locus mutation system in mice, Arch. Toxicol., 38:45–51 (1977).

    Article  Google Scholar 

  49. W. L. Russell, Mutation frequencies in female mice and the estimation of genetic hazards of radiation in women, Proc. Natl. Acad. Sci. USA, 74:3523–3527 (1977).

    Article  ADS  Google Scholar 

  50. F. M. Johnson, G. T. Roberts, R. K. Sharma, F. Chasalow, R. Zweidinger, A. Morgan, R. W. Hendren, and S. E. Lewis, The detection of mutants in mice by electrophoresis: Results of a model induction experiment with procarbazine, Genetics, 97: 113–124 (1981).

    Google Scholar 

  51. E. R. Soares, TEM-Induced gene mutations at enzyme loci in the mouse, Environ. Mutagen., 1:19–25 (1979).

    Article  MathSciNet  Google Scholar 

  52. J. B. Bishop and R. J. Feuers, Development of a new biochemical mutations test in mice based upon measurement of enzyme activities II. Test results with ethyl methanesulfonate (EMS), Mutat. Res., 95:273–285 (1982).

    Article  Google Scholar 

  53. W. L. Russell, E. M. Kelly, P. P. Hunsicker, J. W. Bangham, S. C. Maddux, and E. L. Phipps, Specific-locus test shows ethylnitrosourea to be the most potent mutagen in the mouse, Proc. Natl. Acad. Sci. USA, 76:5818–5819 (1979).

    Article  ADS  Google Scholar 

  54. J. V. Neel, Mutation and disease in man, Canad. J. Genet, and Cytol., 20:295–306 (1978).

    Google Scholar 

  55. C. O. Carter, Contribution of gene mutations to genetic disease in humans, Prog. Mutat. Res., 3:1–8 (1982).

    Google Scholar 

  56. C. O. Carter, in: “Prog. Genetic Toxicol.” D. Scott, B. A. Bridges and F. H. Sobels, eds., pp. 1–14, Elsevier/North Holland Press, Amsterdam (1977).

    Google Scholar 

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Authors and Affiliations

  1. Department of Human Genetics, University of Michigan Medical School, 48109, Ann Arbor, Michigan, USA

    Harvey W. Mohrenweiser

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  1. National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA

    Frederick J. de Serres  & William Sheridan  & 

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Mohrenweiser, H.W. (1983). Biochemical Approaches to Monitoring Human Populations for Germinal Mutation Rates: II. Enzyme Deficiency Variants as a Component of the Estimated Genetic Risk. In: de Serres, F.J., Sheridan, W. (eds) Utilization of Mammalian Specific Locus Studies in Hazard Evaluation and Estimation of Genetic Risk. Environmental Science Research, vol 28. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-3739-3_5

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  • DOI: https://doi.org/10.1007/978-1-4613-3739-3_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-3741-6

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