Towards an Automated Micronucleus Assay as an Internal Dosimeter for Carcinogen-Exposed Human Population Groups

  • H. F. Stich
  • A. B. Acton
  • B. Palcic
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 120)

Abstract

Predictions concerning human responses to carcinogen exposures depend to a large extent on the extrapolation of results obtained from tissue cultures or animal models. Because of differences in the pharmacology of carcinogens in different species, such extrapolations are of restricted value. Furthermore, there is a tendency to compare the effects of high carcinogen doses such as are used in experiments with cultured cells and rodents, with the actions of low doses to which humans are usually exposed. These difficulties can be overcome by using markers which are applicable to cultured cells, animal models and human subjects. We have previously shown that micronuclei are suitable internal dosimeters for revealing tissue-specific genotoxic damage in individuals exposed to carcinogenic mixtures (Stich et al. 1982a, b; Stich 1987; Stich and Rosin 1983, 1985) and for following the response to chemopreventive agents in short-term intervention trials (Stich 1986a, b, 1987; Stich et al. 1984, 1988). In this paper, we place particular emphasis on the automated scoring of micronuclei, which would make this test applicable to large-scale studies of human population groups.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abe T, Isemura T, Kikuchi Y (1984) Micronuclei in human bone-marrow cells: evaluation of the micronucleus test using human leukemia patients treated with antileukemic agents. Mutat Res 130: 113–120PubMedGoogle Scholar
  2. Blakey DH, Duncan AMV, Wargovich MJ, Goldberg MT, Bruce WR, Heddle JA (1985) Detection of nuclear anomalies in the colonic epithelium of the mouse. Cancer Res 45: 242–249PubMedGoogle Scholar
  3. Bruce WR, Heddle JA (1979) The mutagenic activity of 61 different agents as determined by micronucleus, salmonella and sperm anomaly assays. Can J Genet Cytol 21: 319–334PubMedGoogle Scholar
  4. Callisen HH, Pincu M, Norman A (1986) Feasibility of automating the micronucleus assay. Anal Quant Cytol Histol 8: 219–223PubMedGoogle Scholar
  5. Cole RJ, Taylor N, Cole J, Arlett CF (1981) Short-term tests for transplacentally active carcinogens. I. Micronucleus formation in fetal and maternal mouse erythroblasts. Mutat Res 80: 141–157Google Scholar
  6. Fenech M, Morley A (1985a) Solutions to the kinetic problem in the micronucleus assay. Cytobios 43: 233–246PubMedGoogle Scholar
  7. Fenech M, Morley A (1985b) Measurement of micronuclei in lymphocytes. Mutat Res 147: 29–36PubMedGoogle Scholar
  8. Fenech M, Morley A (1986) Cytokinesis-block micronucleus method in human lympho- cytes: effect of in vivo ageing and low dose X-irradiation. Mutat Res 161: 193–198PubMedCrossRefGoogle Scholar
  9. Fontham E, Correa P, Rodriguez E, Lin Y (1986) Validation of smoking history with the micronuclei test. In: Hoffmann D, Harris CC (eds) Mechanisms in tobacco carcinogenesis. Cold Spring Harbor Laboratory, Cold Spring Harbor NY, pp 113–119 (Banbury report 23 )Google Scholar
  10. Henderson L, Cole R, Cole J, Cole H, Aghamohammadi Z, Regan T (1984) Sister-chromatid exchange and micronucleus induction as indicators of genetic damage in maternal and fetal cells. Mutat Res 126: 47–52PubMedCrossRefGoogle Scholar
  11. Högstedt B, Nilsson PG, Mitelman F (1981) Micronuclei in erythropoietic bone marrow cells: relation to cytogenetic pattern and prognosis in acute nonlymphocytic leukemia. Cancer Genet Cytogenet 3: 185–193PubMedCrossRefGoogle Scholar
  12. Högstedt B, Akesson B, Axell K, Gullberg B, Mitelman F, Pero RW, Skerfving S, Welinder H (1983) Increased frequency of lymphocyte micronuclei in workers producing reinforced polyester resin with low exposure to styrene. Scand J Work Environ Health 49: 271–276Google Scholar
  13. Jaggi B, Deen MJ, Palcic B (1989) Design of a Solid State Microscope. Opt Eng 28: 675–687Google Scholar
  14. Jenssen D, Ramel C (1980) The micronucleus test as part of a short-term mutagenicity test program for the prediction of carcinogenicity evaluated by 143 agents tested. Mutat Res 75: 191–192PubMedGoogle Scholar
  15. Lähdetie J (1986) Micronucleated spermatids in the seminal fluid of smokers and nonsmokers. Mutat Res 172: 255–263PubMedCrossRefGoogle Scholar
  16. MacGregor JT, Wehr CM, Langlois RG (1983) A simple fluorescent staining procedure for micronuclei and RNA in erythrocytes using Hoechst 33258 and pyronin Y. Mutat Res 120: 269–275PubMedCrossRefGoogle Scholar
  17. Mandard AM, Duigou F, Marnay J, Masson P, Qiu SL, Yi JS, Barrellier P, Lebigot G (1987) Analysis of the results of the micronucleus test in patients presenting upper digestive tract cancers and in non-cancerous subjects. Int J Cancer 39: 442–444PubMedCrossRefGoogle Scholar
  18. Meretoja T, Järventaus H, Sorsa M, Vainio H (1978) Chromosome aberrations in lymphocytes of workers exposed to styrene. Scand J Work Environ Health 4 [Suppl 2]: 259–264PubMedCrossRefGoogle Scholar
  19. Munoz N, Hayashi M, Lu JB, Wahrendorf J, Crespi M, Bosch FX (1987) Effect of riboflavin, retinol, and zinc on micronuclei of buccal mucosa and of esophagus: a randomized double-blind intervention study in China. JNCI 79: 687–691PubMedGoogle Scholar
  20. Nordenson I, Beckman L (1984) Chromosomal aberrations in lymphocytes of workers exposed to low levels of styrene. Hum Hered 34: 178–182PubMedCrossRefGoogle Scholar
  21. Palcic B, Jaggi B (1990) Image cytometry system for morphometric measurements of live cells. In: Wise DL (ed) Bioinstrumentation: developments and applications. Butterworth, Stoneham MD (in press)Google Scholar
  22. Parvez Z, Kormano M, Satokari K, Moncada R, Eklund R (1987) Induction of mitotic micronuclei by X-ray contrast media in human peripheral lymphocytes. Mutat Res 188: 233–239PubMedCrossRefGoogle Scholar
  23. Picker JD, Fox DP (1986) Do curried foods produce micronuclei in buccal epithelial cells? Mutat Res 171: 185–188PubMedCrossRefGoogle Scholar
  24. Raafat M, El-Gerzawi S, Stich HF (1984) Detection of mutagenicity in urothelial cells of bilharzial patients by “the micronucleus test”. J Egypt Natl Cancer Inst 1: 63–73Google Scholar
  25. Rabello-Gay MN, Carvalho MI, Otto PA, Targa HJ (1985) The effects of age, sex and diet on the clastogenic action of cyclophosphamide in mouse bone marrow. Mutat Res 158: 181–188PubMedCrossRefGoogle Scholar
  26. Reali D, DiMarino F, Bahramandpour S, Carducci A, Barale R, Loprieno N (1987) Micronuclei in exfoliated urothelial cells and urine mutagenicity in smokers. Mutat Res 192: 145–149PubMedCrossRefGoogle Scholar
  27. Ronen A, Heddle JA (1984) Site-specific induction of nuclear anomalies (apoptotic bodies and micronuclei) by carcinogens in mice. Cancer Res 44: 1536–1540PubMedGoogle Scholar
  28. Rosin MP, German J (1985) Evidence for chromosome instability in vivo in- Bloom syndrome: increased numbers of micronuclei in exfoliated cells. Hum Genet 71: 187–191PubMedCrossRefGoogle Scholar
  29. Rosin MP, Ochs HD (1986) In vivo chromosomal instability in ataxia-telangiectasia homozygotes and heterozygotes. Hum Genet 74: 335–340PubMedCrossRefGoogle Scholar
  30. Schlegel R, MacGregor JT (1984) The persistence of micronucleated erythrocytes in the peripheral circulation of normal and splenectomized Fischer 344 rats: implications for cytogenetic screening. Mutat Res 127: 169–174PubMedCrossRefGoogle Scholar
  31. Stich HF (1986a) The use of micronuclei in tracing the genotoxic damage in the oral mucosa of tobacco users. In: Hoffmann D, Harris CC (eds) Mechanisms in tobacco carcinogenesis. Cold Spring Harbor Laboratory, Cold Spring Harbor NY, pp 99–111 (Banbury report 23 )Google Scholar
  32. Stich HF (1986b) Reducing the genotoxic damage in the oral mucosa of betel quid/tobacco chewers. In: Shankel DM et al. (eds) Antimutagenesis and anticarcinogenesis mechanisms. Plenum, New York, pp 381–391Google Scholar
  33. Stich HF (1987) Micronucleated exfoliated cells as indicators for genotoxic damage and as markers in chemoprevention trials. J Nutr Growth Cancer 4: 9–18Google Scholar
  34. Stich HF, Rosin MP (1983) Quantitating the synergistic effect of smoking and alcohol consumption with the micronucleus test on human buccal mucosa cells. Int J Cancer 31: 305–308PubMedCrossRefGoogle Scholar
  35. Stich HF, Rosin MP (1985) Towards a more comprehensive evaluation of a genotoxic hazard in man. Mutat Res 150: 43–50PubMedCrossRefGoogle Scholar
  36. Stich HF, Yohn DS (1970) Viruses and chromosomes. Prog Med Virol 12: 78–127 Stich HF, Curtis JR, Parida BB (1982a) Application of the micronucleus test to exfoliated cells of high cancer risk groups: tobacco chewers. Int J Cancer 30: 553–559CrossRefGoogle Scholar
  37. Stich HF, Stich W, Parida BB (1982b) Elevated frequency of micronucleated cells in the buccal mucosa of individuals at high risk for oral cancer: betel quid chewers. Cancer Lett 17: 125–134PubMedCrossRefGoogle Scholar
  38. Stich HF, Stich W, Rosin MP, Vallejera MO (1984) Use of the micronucleus test to monitor the effect of vitamin A, beta-carotene and canthaxanthin on the buccal mucosa of betel nut/tobacco chewers. Int J Cancer 34: 745–750PubMedCrossRefGoogle Scholar
  39. Stich HF, Hornby AP, Dunn BP (1985) A pilot beta-carotene intervention trial with Inuits using smokeless tobacco. Int J Cancer 36: 321–327PubMedGoogle Scholar
  40. Stich HF, Rosin MP, Hornby AP, Mathew B, Sankaranarayanan R, Krishnan Nair M (1988) Remission of oral leukoplakias and micronuclei in tobacco/betel quid chewers treated with beta-carotene and with beta-carotene plus vitamin A. Int J Cancer 42: 195–199PubMedCrossRefGoogle Scholar
  41. Wargovich MJ, Goldberg MT, Newmark HL, Bruce WR (1983) Nuclear aberrations as a short-term test for genotoxicity to the colon: evaluation of nineteen agents in mice. JNCI 71: 133–137PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin·Heidelberg 1990

Authors and Affiliations

  • H. F. Stich
    • 1
  • A. B. Acton
    • 1
  • B. Palcic
    • 1
  1. 1.Environmental Carcinogenesis Unit, and Cancer Imaging SectionBritish Columbia Cancer Research CentreVancouverCanada

Personalised recommendations