Does Radiation Cause Chromosome Breakage?

Ionizing radiation is known to cause chromosomal damage, which can lead to aneuploidy and other genetic mutations. This damage can be detected in vitro using human cell lines or lymphocytes treated with the test substance, both with and without metabolic activation. The damage is evaluated by measuring the number of binucleate cells in the first interphase cell after exposure. Cytochalasin B is a compound that blocks cytokinesis (cytoplasmic division) without affecting nuclear division.

It is used to identify binucleate cells, which are then used as an indicator of xenobiotic-induced cytotoxicity. Micronuclei are formed from acentric fragments of chromosomes or whole chromosomes that are not included in the main nucleus of the interphase cell. Variations of this methodology have also been used to evaluate mechanisms induced by test articles. An immunostaining technique is used to differentiate micronuclei containing kinetochores, thus evaluating the aneugenic potential of a test substance.

Exposure to ionizing radiation (IR) can cause chromosomal breaks, which can lead to cell death, chromosomal rearrangements, and genome instability. We have identified a role for H3K36me3 in homologous recombination repair of double-stranded DNA breaks, and its loss sensitizes cells to ionizing radiation. In addition, the loss of H3K36me3 was found to be synthetic lethal with WEE1 inactivation, identifying a role for SETD2 in facilitating the restart of DNA replication and defining that WEE1 inhibition causes CDK-induced replication stress. Therefore, we have focused on delineating the role of the H3K36me3 pathway in repairing homologous recombination; determining how H3K36me3 maintains viability in response to replication stress; and translating our findings to the clinic, using both fission yeast and human cellular systems.

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