What are the causes and effects of radiation on chromosomes?

When cells are exposed to radiation or carcinogens, DNA sometimes breaks and broken ends can rejoin in patterns different from their original arrangement. The abnormalities that occur are called “chromosomal aberrations” and can be visualized in mitosis when cells divide. This assay detects chromosomal damage in vitro using human cell lines or lymphocytes treated with the test substance both in the presence and absence of metabolic activation (Figure 27,. Chromosomal damage is evaluated as an increase in the number of micronucleated cells in the first interphase cell after exposure (Krishna et al.

This cell population is identified as binucleate cells (2 nuclei) when cytochalasin B is used during testing. Cytochalasin B is a compound that has been shown to block cytokinesis (cytoplasmic division) without affecting nuclear division. Relative changes in the proportion of binucleate cells in treated cultures compared to control cultures can be used as an indicator of xenobiotic-induced cytotoxicity. Micronuclei (small nuclei) are formed from acentric fragments of chromosomes (clastogenic mechanism) or whole chromosomes (aneugenic mechanism) that are not included in the main nucleus of the interphase cell (Krishna et al.

Variations of this methodology have also been used for mechanisms induced by test articles (Krishna et al. An immunostaining technique is used to differentiate micronuclei containing kinetochore (s), thus evaluating the aneugenic potential of a test substance (shown in Figure 27,. With densely ionizing radiation, in comparison, the performance of double-break aberrations for a given dose is greater than with sparsely ionizing radiation and is proportional to dose regardless of dose rate.

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