Methods to Estimate the Genetic Risk

  • U. H. Ehling

Abstract

In this chapter those effects are considered that may be inherited through radiation- or chemically-induced injury to the genes or chromosomes of germ cells. Mutational changes represent a broad spectrum of alterations in the deoxyribonucleotide structure of the genes. At one end of the spectrum this change can be represented by a single nucleotide base substitution, base addition or deletion. At the other end of the mutation spectrum is a complete deletion of the entire gene and/or adjacent genes. For higher organisms these submicroscopic changes are not further resolvable in many instances, and they are simply classified as mutations.

Keywords

Methane Cage Recombination Germinal Fractionation 

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References

  1. Abrahamson S, Bender MA, Conger AD, Wolff S (1973) Uniformity of radiation-induced mutation rates among different species. Nature 245:460–462PubMedCrossRefGoogle Scholar
  2. Bartsch-Sandhoff M (1974) Skeletal abnormalities in mouse embryos after irradiation of the sire. Humangenetik 25:93–100PubMedCrossRefGoogle Scholar
  3. Bateman AJ (1979) Significance of specific-locus germ-cell mutations in mice. Mutat Res 64: 345–351PubMedGoogle Scholar
  4. BEIR-Report (1972) (Biological Effects of Ionizing Radiations) The effects on populations of exposure to low levels of ionizing radiation. National Academy, Washington, D.C.Google Scholar
  5. BEIR-Report (1980) (Biological Effects of Ionizing Radiations) The effects on populations of exposure to low levels of ionizing radiation: 1980. National Academy, Washington, D.C.Google Scholar
  6. BMI (Bundesministerium des Innern) Umweltradioaktivität und Strahlenbelastung. Jahresbericht 1979Google Scholar
  7. Brown KS, Cranley RE, Greene R, Kleinman HK, Pennypacker JP (1981) Disproportionate micromelia (Dmm): An incomplete dominant mouse dwarfism with abnormal cartilage matrix. J Embryol Exp Morphol 62:165–182PubMedGoogle Scholar
  8. Cattanach BM (1966) Chemically induced mutations in mice. Mutat Res 3:346–353PubMedCrossRefGoogle Scholar
  9. Cattanach BM (1971) Specific locus mutation in mice. In: Hollaender A (ed) Chemical mutagens; principles and methods for their detection, vol 2. Plenum, New York, pp 535–539Google Scholar
  10. Cattanach BM (1982) Induction of specific-locus mutations in female mice by triethylenemelamine (TEM). Mutat Res 104:173–176PubMedCrossRefGoogle Scholar
  11. CCEM-Report (1983) (Committee on Chemical Environmental Mutagens) Identifying and estimating the genetic impact of chemical mutagens. National Academy, Washington, D.C.Google Scholar
  12. Crow JF (1981) How well can we assess genetic risks? Not very. In: Lauriston S Taylor lectures in radiation protection and measurements, lecture no. 5. National Council on Radiation Protection and Measurements, Washington, D.C., pp 7–31 (quotation p 13)Google Scholar
  13. Ehling U (1963) Vererbung von Augenleiden im Tierreich. Bericht über die 65. Zusammenkunft der Deutschen Ophthalmologischen Gesellschaft in Heidelberg. Bergmann, München, 228–238Google Scholar
  14. Ehling UH (1965) The frequency of X-ray induced dominant mutations affecting the skeleton of mice. Genetics 51:723–732PubMedGoogle Scholar
  15. Ehling UH (1966) Dominant mutations affecting the skeleton in offspring of X-irradiated male mice. Genetics 54:1381–1389PubMedGoogle Scholar
  16. Ehling UH (1970) Evaluation of presumed dominant skeletal mutations. In: Vogel F, Röhrborn G (eds) Chemical mutagenesis in mammals and man. Springer, Berlin Heidelberg New York, pp 162–166Google Scholar
  17. Ehling UH (1974) Die Gefährdung der menschlichen Erbanlagen im technischen Zeitalter (Vortrag beim Deutschen Röntgenkongreß 1974 in Baden-Baden). Fortschr Röntgenstr 124:166 to 171 (1976)PubMedGoogle Scholar
  18. Ehling UH (1976) Estimation of the frequency of radiation-induced dominant mutations. ICRP, CI-TG 14, Task Group on Genetically Determined Ill-HealthGoogle Scholar
  19. Ehling UH (1977) Dominant lethal mutations in male mice. Arch Toxicol 38:1–11PubMedCrossRefGoogle Scholar
  20. Ehling UH (1978) Specific-locus mutations in mice. In: Hollaender A, de Serres FJ (eds) Chemical mutagens, principles and methods for their detection, vol 5. Plenum, New York, pp 233 to 256Google Scholar
  21. Ehling UH (1979) Criteri di stima del rischio genetico. In: Enciclopedia della scienza e della tecnica. Mondadori, Milano, pp 125–134Google Scholar
  22. Ehling UH (1980a) Induction of gene mutations in germ cells of the mouse. Arch Toxicol 46: 123–138PubMedCrossRefGoogle Scholar
  23. Ehling UH (1980b) Strahlengenetisches Risiko des Menschen. Umschau 80:754–759Google Scholar
  24. Ehling UH (1981) Genetische Risiken durch Umweltchemikalien. In: Glöbel B, Gerber G, Grillmaier R, Kunkel R, Leetz H-K, Oberhausen E (Hrsg) Umweltrisiko 80. Thieme, Stuttgart New York, pp 400–411Google Scholar
  25. Ehling UH (1982) Risk estimations based on germ-cell mutations in mice. In: Sugimura T, Kondo S, Takebe H (eds) Environmental mutagens and carcinogens (Proceedings of the 3rd International Conference on Environmental Mutagens). University of Tokyo Press, Tokyo New York, pp 709–719Google Scholar
  26. Ehling UH (in press) In vivo gene mutations in mammals. Proceedings of the symposium “Critical evaluation of mutagenicity tests”. Bundesgesundheitsamt, BerlinGoogle Scholar
  27. Ehling UH, Neuhäuser A (1979) Procarbazine-induced specific-locus mutations in male mice. Mutat Res 59:245–256PubMedCrossRefGoogle Scholar
  28. Ehling UH, Neuhäuser-Klaus A (1982) Chemically-induced mutations in mice, Progress report: Mai 1982-November 1982. Commission of the European CommunitiesGoogle Scholar
  29. Ehling UH, Randolph ML (1962) Skeletal abnormalities in the Fl generation of mice exposed to ionizing radiations. Genetics 47:1543–1555PubMedGoogle Scholar
  30. Ehling UH, Favor J, Kratochvilova J, Neuhäuser-Klaus A (1982) Dominant cataract mutations and specific-locus mutations in mice induced by radiation or ethylnitrosourea. Mutat Res 92: 181–192PubMedCrossRefGoogle Scholar
  31. Ehling UH, Averbeck D, Cerutti PA, Friedman J, Greim H, Kolbye Jr AC, Mendelsohn ML (1983) Review of the evidence for the presence or absence of thresholds in the induction of genetic effects by genotoxic chemicals. Mutat Res 123:281–341PubMedGoogle Scholar
  32. Favor J (1982a) The penetrance value tested of a presumed dominant mutation heterozygote in a genetic confirmation test for a given number of offspring observed. Mutat Res 92:192Google Scholar
  33. Favor J (1982b) The dominant cataract mutation test in mice. Mutat Res 97:186–187Google Scholar
  34. Favor J (1983) A comparison of the dominant cataract and recessive specific-locus mutation rates induced by treatment of male mice with ethylnitrosourea. Mutat Res 110:367–382PubMedCrossRefGoogle Scholar
  35. Glubrecht H, Gopal-Ayengar AR, Ehrenberg L (1979) Interactions of ionizing radiation and chemicals and mechanisms of action - summary. In: Okada S, Imamura M, Terashima T, Yamaguchi H (eds) Radiation research. Proceedings of the 6th International Congress of Radiation Research. Japanese Association for Radiation Research, Tokyo, Japan, pp 708–710Google Scholar
  36. Green MC (1966) Mutant genes and linkages. In: Green EL (ed) Biology of the laboratory mouse, 2nd edn. McGraw Hill, New York, pp 87–150Google Scholar
  37. Heller CG, Clermont Y (1964) Kinetics of the germinal epithelium in man. In: Pincus G (ed) Recent progress in hormone research. Academic, New York London, pp 545–575Google Scholar
  38. Jacobi W, Paretzke HG, Ehling UH (1981) Strahlenexposition und Strahlenrisiko der Bevölkerung. GSF-Bericht, S-710Google Scholar
  39. Kada T, Inoue T, Yokoiyama A, Russell LB (1979) Combined genetic effects of chemicals and radiation. In: Okada S, Imamura M, Terashima T, Yamaguchi H (eds) Radiation research. Proceedings of the 6th International Congress of Radiation Research. Japanese Association for Radiation Research, Tokyo, Japan, pp 711–720Google Scholar
  40. Kirk M, Lyon MF (1982) Induction of congenital anomalies in offspring of female mice exposed to varying doses of X-rays. Mutat Res 106:73–83PubMedCrossRefGoogle Scholar
  41. Kratochvilova J (1981) Dominant cataract mutations detected in offspring of gamma-irradiated male mice. J Hered 72:302–307PubMedGoogle Scholar
  42. Kratochvilova J, Ehling UH (1979) Dominant cataract mutations induced by yirradiation of male mice. Mutat Res 63:221–223PubMedCrossRefGoogle Scholar
  43. Laskowski W (1981) Biologische Strahlenschäden und ihre Reparatur. De Gruyter, Berlin New YorkGoogle Scholar
  44. Lüning KG, Searle AG (1971) Estimates of the genetic risks from ionizing iiradiation. Mutat Res 12:291–304PubMedCrossRefGoogle Scholar
  45. McKusick VA (1978) Mendelian inheritance in man, 5th edn. Johns Hopkins University Press, BaltimoreGoogle Scholar
  46. Muller HJ (1950) Radiation damage to the genetic material. Am Sci 38:33–59Google Scholar
  47. Neuhäuser-Klaus A (1983) Personal communicationGoogle Scholar
  48. Nomura T (1982) Parental exposure to X rays and chemicals induces heritable tumours and anomalies in mice. Nature 296:575–577PubMedCrossRefGoogle Scholar
  49. Oakberg EF (1956) Duration of spermatogenesis in the mouse and timing of stages of the cycle of the seminiferous epithelium. Am J Anat 99:507–516PubMedCrossRefGoogle Scholar
  50. Roderick TH (1964) Proceedings of the symposium: The effects of radiation on the hereditary fitness of mammalian populations. The Jackson Laboratory, Bar Harbor, Maine, June 29 to July 1, 1964. Genetics 50:1023–1217Google Scholar
  51. Russell LB, Selby PB, von Halle E, Sheridan W, Valcovic L (1981) The mouse specific-locus test with agents other than radiations. Interpretation of data and recommendations for future work. Mutat Res 86:329–354PubMedGoogle Scholar
  52. Russell WL (1951) X-ray-induced mutations in mice. Cold Spring Harbor Symp Quant Biol 16: 327–336PubMedGoogle Scholar
  53. Russell WL (1972) The genetic effects of radiation. In: Peaceful uses of atomic energy, vol 13. International Atomic Energy Agency, Vienna, pp 487–500Google Scholar
  54. Russell WL (1977) Mutation frequencies in female mice and the estimation of genetic hazards of radiation in women. Proc Natl Acad Sci USA 74:3523–3527PubMedCrossRefGoogle Scholar
  55. Russell WL, Kelly EM (1982) Mutation frequencies in male mice and the estimation of genetic hazards of radiation in men. Proc Natl Acad Sci USA 79:542–544PubMedCrossRefGoogle Scholar
  56. Russell WL, Hunsicker PR, Carpenter DA, Cornett CV, Guinn GM (1982) Effect of dose fractionation on the ethylnitrosourea induction of specific-locus mutations in mouse spermatogonia. Proc Natl Acad Sci USA 79:3592–3593PubMedCrossRefGoogle Scholar
  57. Russell WL, Kelly EM, Hunsicker PR, Bangham JW, Maddux SC, Phipps EL (1979) Specificlocus test shows ethylnitrosourea to be the most potent mutagen in the mouse. Proc Natl Acad Sci USA 76:5818–5819PubMedCrossRefGoogle Scholar
  58. Sankaranarayanan K (1982) Genetic effects of ionizing radiation in multicellular eukaryotes and the assessment of genetic radiation hazards in man. Elsevier Biomedical, Amsterdam (quotations p 276, p 311)Google Scholar
  59. Schull WJ, Otake M, Neel JV (1981) Genetic effects of the atomic bombs: a reappraisal. Science 213:1220–1227 (quatotation p 1227)PubMedCrossRefGoogle Scholar
  60. Searle AG (1974) Mutation induction in mice. In: Lett JT, Adler HI, Zelle M (eds) Advances in radiation biology, vol 4. Academic, New York London, pp 131–207Google Scholar
  61. Searle AG (1975) The specific locus test in the mouse. Mutat Res 31:277–290PubMedGoogle Scholar
  62. Selby PB (1979) Induced skeletal mutations. Genetics 92:S127-S133Google Scholar
  63. Selby PB, Selby PR (1977) Gamma-ray-induced dominant mutations that cause skeletal abnormalities in mice. I. Plan, summary of results and discussion. Mutat Res 43:357–375PubMedCrossRefGoogle Scholar
  64. Setchell BP (1970) Testicular blood supply, lymphatic drainage, and secretion of fluid. In: Johnson AD, Gomes WR, VanDemark NL (eds) The testis, vol 1. Academic, New York, pp 101 to 239Google Scholar
  65. Snow CP (1964) The two cultures: And a second look. University Press, Cambridge (quotation P7)Google Scholar
  66. Stevenson AC (1959) The load of hereditary defects in human populations. Radiat Res Suppl 1:306–325CrossRefGoogle Scholar
  67. Trimble BK, Doughty JH (1974) The amount of hereditary disease in human populations. Ann Hum Genet 38:199–223PubMedCrossRefGoogle Scholar
  68. UNSCEAR-Report (1966) (United Nations Scientific Committee on the Effects of Atomic Radiation) Supplement no 14. United Nations, New YorkGoogle Scholar
  69. UNSCEAR-Report (1977) (United Nations Scientific Committee on the Effects of Atomic Radiation) Sources and effects of ionizing radiation. United Nations, New YorkGoogle Scholar
  70. UNSCEAR-Report (1982) (United Nations Scientific Committee on the Effects of Atomic Radiation) Ionizing radiation: Sources and biological effects. United Nations, New YorkGoogle Scholar
  71. Wolff S (1967) Radiation genetics. In: Roman HL, Sandler LM, Stent GS (eds) Annual review of genetics, vol 1. Annual Reviews, Inc, Palo Alto, California, pp 221–244Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1984

Authors and Affiliations

  • U. H. Ehling
    • 1
  1. 1.Institut für GenetikGesellschaft für Strahlen- und Umweltforschung (GSF)NeuherbergGermany

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