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. 1996 May;104(Suppl 3):445–448. doi: 10.1289/ehp.96104s3445

Current cytogenetic methods for detecting exposure and effects of mutagens and carcinogens.

A T Natarajan 1, J J Boei 1, F Darroudi 1, P C Van Diemen 1, F Dulout 1, M P Hande 1, A T Ramalho 1
PMCID: PMC1469636  PMID: 8781361

Abstract

Most mutagens and genotoxic carcinogens are efficient inducers of chromosomal alterations in exposed cells. Two important classes of aberrations, namely structural and numerical, are recognized and both types of aberrations are associated with congenital abnormalities and neoplasia in humans. These alterations can be easily detected and quantified in human peripheral blood lymphocytes. Conventional staining techniques can be used to detect these aberrations; this technique was used to estimate absorbed dose in the case of a radiation accident in Goiania, Brazil. A recently introduced fluorescent in situ hybridization technique (FISH) using DNA probes has increased the sensitivity and ease of detecting chromosome aberrations, especially stable chromosome aberrations. This technique allows, to some extent, the estimation of absorbed radiation dose from past exposures. Numerical aberrations can be directly estimated in metaphases by counting the number of FISH-painted chromosomes. Micronuclei are formed by lagging chromosome fragments or whole chromosomes during the anaphase stage of cell division. The nature of micronuclei as to whether they possess a centromere can be determined either by CREST staining (calcinosis, Raynoud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) or FISH with centromere-specific DNA probes. In several carcinogen-exposed populations, such as heavy smokers or people exposed to arsenic, aneuploidy appears to be more common than structural aberrations. In victims of radiation accidents, aneuploidy (hyperploidy) has been found to be common in addition to structural aberrations.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Balajee A. S., Domínguez I., Natarajan A. T. Construction of Chinese hamster chromosome specific DNA libraries and their use in the analysis of spontaneous chromosome rearrangements in different cell lines. Cytogenet Cell Genet. 1995;70(1-2):95–101. doi: 10.1159/000134000. [DOI] [PubMed] [Google Scholar]
  2. Boei J. J., Balajee A. S., de Boer P., Rens W., Aten J. A., Mullenders L. H., Natarajan A. T. Construction of mouse chromosome-specific DNA libraries and their use for the detection of X-ray-induced aberrations. Int J Radiat Biol. 1994 May;65(5):583–590. doi: 10.1080/09553009414550671. [DOI] [PubMed] [Google Scholar]
  3. Boei J. J., Natarajan A. T. Detection of chromosome malsegregation to the daughter nuclei in cytokinesis-blocked transgenic mouse splenocytes. Chromosome Res. 1995 Jan;3(1):45–53. doi: 10.1007/BF00711161. [DOI] [PubMed] [Google Scholar]
  4. Carrano A. V., Natarajan A. T. International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC publication no. 14. Considerations for population monitoring using cytogenetic techniques. Mutat Res. 1988 Mar;204(3):379–406. doi: 10.1016/0165-1218(88)90036-5. [DOI] [PubMed] [Google Scholar]
  5. Fenech M., Morley A. A. Cytokinesis-block micronucleus method in human lymphocytes: effect of in vivo ageing and low dose X-irradiation. Mutat Res. 1986 Jul;161(2):193–198. doi: 10.1016/0027-5107(86)90010-2. [DOI] [PubMed] [Google Scholar]
  6. Hagmar L., Brøgger A., Hansteen I. L., Heim S., Högstedt B., Knudsen L., Lambert B., Linnainmaa K., Mitelman F., Nordenson I. Cancer risk in humans predicted by increased levels of chromosomal aberrations in lymphocytes: Nordic study group on the health risk of chromosome damage. Cancer Res. 1994 Jun 1;54(11):2919–2922. [PubMed] [Google Scholar]
  7. Lucas J. N., Awa A., Straume T., Poggensee M., Kodama Y., Nakano M., Ohtaki K., Weier H. U., Pinkel D., Gray J. Rapid translocation frequency analysis in humans decades after exposure to ionizing radiation. Int J Radiat Biol. 1992 Jul;62(1):53–63. doi: 10.1080/09553009214551821. [DOI] [PubMed] [Google Scholar]
  8. Natarajan A. T., Obe G. Screening of human populations for mutations induced by environmental pollutants: use of human lymphocyte system. Ecotoxicol Environ Saf. 1980 Dec;4(4):468–481. doi: 10.1016/0147-6513(80)90049-4. [DOI] [PubMed] [Google Scholar]
  9. Natarajan A. T., Vyas R. C., Darroudi F., Vermeulen S. Frequencies of X-ray-induced chromosome translocations in human peripheral lymphocytes as detected by in situ hybridization using chromosome-specific DNA libraries. Int J Radiat Biol. 1992 Feb;61(2):199–203. doi: 10.1080/09553009214550821. [DOI] [PubMed] [Google Scholar]
  10. Natarajan A. T., Vyas R. C., Wiegant J., Curado M. P. A cytogenetic follow-up study of the victims of a radiation accident in Goiania (Brazil). Mutat Res. 1991 Mar;247(1):103–111. doi: 10.1016/0027-5107(91)90038-p. [DOI] [PubMed] [Google Scholar]
  11. Pinkel D., Straume T., Gray J. W. Cytogenetic analysis using quantitative, high-sensitivity, fluorescence hybridization. Proc Natl Acad Sci U S A. 1986 May;83(9):2934–2938. doi: 10.1073/pnas.83.9.2934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ramalho A. T., Curado M. P., Natarajan A. T. Lifespan of human lymphocytes estimated during a six year cytogenetic follow-up of individuals accidentally exposed in the 1987 radiological accident in Brazil. Mutat Res. 1995 Sep;331(1):47–54. doi: 10.1016/0027-5107(95)00049-o. [DOI] [PubMed] [Google Scholar]
  13. Rupa D. S., Hasegawa L., Eastmond D. A. Detection of chromosomal breakage in the 1cen-1q12 region of interphase human lymphocytes using multicolor fluorescence in situ hybridization with tandem DNA probes. Cancer Res. 1995 Feb 1;55(3):640–645. [PubMed] [Google Scholar]
  14. Sasaki M. S., Miyata H. Biological dosimetry in atomic bomb survivors. Nature. 1968 Dec 21;220(5173):1189–1193. doi: 10.1038/2201189a0. [DOI] [PubMed] [Google Scholar]
  15. Schmid E., Zitzelsberger H., Braselmann H., Gray J. W., Bauchinger M. Radiation-induced chromosome aberrations analysed by fluorescence in situ hybridization with a triple combination of composite whole chromosome-specific DNA probes. Int J Radiat Biol. 1992 Dec;62(6):673–678. doi: 10.1080/09553009214552621. [DOI] [PubMed] [Google Scholar]
  16. Vahter M., Concha G., Nermell B., Nilsson R., Dulout F., Natarajan A. T. A unique metabolism of inorganic arsenic in native Andean women. Eur J Pharmacol. 1995 Dec 7;293(4):455–462. doi: 10.1016/0926-6917(95)90066-7. [DOI] [PubMed] [Google Scholar]
  17. Vyas R. C., Darroudi F., Natarajan A. T. Radiation-induced chromosomal breakage and rejoining in interphase-metaphase chromosomes of human lymphocytes. Mutat Res. 1991 Jul;249(1):29–35. doi: 10.1016/0027-5107(91)90130-g. [DOI] [PubMed] [Google Scholar]
  18. van Diemen P. C., Maasdam D., Vermeulen S., Darroudi F., Natarajan A. T. Influence of smoking habits on the frequencies of structural and numerical chromosomal aberrations in human peripheral blood lymphocytes using the fluorescence in situ hybridization (FISH) technique. Mutagenesis. 1995 Nov;10(6):487–495. doi: 10.1093/mutage/10.6.487. [DOI] [PubMed] [Google Scholar]

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