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Concept
Clastogen
Summary
A clastogen is a mutagenic agent that disturbs normal DNA related processes or directly causes DNA strand breakages, thus causing the deletion, insertion, or rearrangement of entire chromosome sections. 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, actinomycin D, camptothecin, methotrexate, methyl acrylate, resorcinol and 5-fluorodeoxyuridine. 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 germ cells that lead to fetus developmental defects.
There is not one all encompassing method by which clastogens damage chromosomal DNA, instead different clastogens have unique ways they interact with DNA, or DNA associated proteins, and disrupt normal function. Broadly these different types of clastogenic activity can be organized into three classes: ‘classic’ breaks theory; ‘mis-repair of breaks’ theory and ‘repair-created breaks’ theory. It may not always be known how a clastogen causes chromosomal damage.
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 alkylating agents which do not break DNA at all, but instead form DNA adducts, and these have often eluded the common theories for DNA breaks leading to misrepair.
Official source
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