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A clastogen is a agent that disturbs normal DNA related processes or directly causes DNA strand breakages, thus causing the deletion, insertion, or rearrangement of entire chromosome sections. (2025). 9783642164828, Springer Berlin Heidelberg. ISBN 9783642164828 These processes are a form of mutagenesis which if left unrepaired, or improperly repaired, can lead to cancer. Known clastogens include acridine yellow, benzene, ethylene oxide, arsenic, phosphine, mimosine, Dactinomycin, camptothecin, methotrexate, methyl acrylate, resorcinol and Floxuridine. Additionally, 1,2-dimethylhydrazine is a known colon carcinogen and shows signs of possessing clastogenic activity. There are many clastogens not listed here and research is ongoing to discover new clastogens. Some known clastogens only exhibit clastogenic activity in certain cell types, such as caffeine which exhibits clastogenic activity in plant cells. Researchers are interested in clastogens for researching cancer, as well as for other human health concerns such as the inheritability of clastogen effected paternal that lead to fetus developmental defects.
Radiation was the earliest known clastogen that caused direct DNA damage, following the classic breaks theory. DNA is frequently damaged and there are many DNA repair pathways that combat this, but repair does not always work perfectly resulting in mistakes (called a misrepair). A widely studied class of clastogens are Alkylation agents which do not break DNA at all, but instead form , and these have often eluded the common theories for DNA breaks leading to misrepair. The final theory encompasses clastogens that do not interact with DNA but instead impair DNA synthesis or DNA repair causing damage to occur through loss of normal function of the protein.
Clastogen damage in certain areas of the chromosome can lead to instability, such as loss or damage to . Studies have shown that rat cells that were exposed to chemical clastogens express telomeric irregularities in function and can remain for several cell generations after treatment has been attempted.
There have been studies done that work with the usage of the deletion (DEL) assay to screen for clastogens.
The micronucleus test is another type of assay that uses gut cells to observe clastogens, and there are a few different types. The micronucleus test on gut cells is useful because in the case of the bone marrow micronucleus test there is not much activity seen after there has been oral exposure therefore more activity is seen in the gut cells. In vitro micronucleus assay (IVMN) can screen for clastogen activity, this method is useful because it can pick up clastogen activity and be used to foresee chromosome aberration activity. The IVMN assay can pick up on fragments that were membrane bound to DNA that were split from nuclei throughout the process of cell division.
These assays are time-consuming so novel methods for monitoring clastogens and aneuploidogens are highly desirable. One example is the use of the monochromosomal hybrid cell for the detection of mis-segregating chromosomes.
In addition, studies have shown that rat cells that were exposed to chemical clastogens express telomeric irregularities in function and can remain for several cell generations after treatment has been attempted.
In plants and mice cells studies have found that purine receptor adenosine, ATP, ADP, cyclohexyladenosine, phenylisopropyladenosine and dimethylaminopurine riboside can lower the amount of clastogen damage seen in and reduce the amount of Micronucleus affected brought on by ethyl methanesulfonate and cyclophosphamide. Some more than others can stop or reduce the clastogen activity of ethyl methanesulfonate such as adenosine, ADP or DAP.
In a study where rats were treated with Brevetoxin B (PbTx2), there was a noticeable 2-3 fold growth in the amount of DNA seen in comet tails which tell us that Brevetoxin B shows in vivo clastogenic activity. This clastogen activity was seen after Brevetoxin B was injected by way of intratracheal administering in the rat.
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