Current cytogenetic methods for detecting exposure and effects of mutagens and carcinogens.
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.
Natarajan
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MGC Department of Radiation Genetics and Chemical Mutagenesis, Leiden University, The Netherlands. natarajan@rullf2.medfac.leidenuniv.nl
Boei
J J
JJ
Darroudi
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Van Diemen
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PC
Dulout
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Hande
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MP
Ramalho
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D000818:Animals; D015197:Carcinogenicity Tests; D002869:Chromosome Aberrations; D003582:Cytogenetics / Q000379:methods*; D004781:Environmental Exposure; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D011839:Radiation, Ionizing