This chapter discusses the role of DNA damage and repair in Neurotoxicity caused by cancer therapies. These therapies include ionizing radiation, the platinum compounds, alkylating agents such as cyclophosphamide and temozolomide, and the topoisomerase interacting agent doxorubicin. Ionizing radiation produces reactive oxygen species (ROS) which in turn can cause oxidative DNA damage. Platinum compounds interact with DNA to form cross-linking adducts. Recent evidence also suggests that platinum compounds increase production of ROS which can damage DNA and contribute to neurotoxicity. Alkylating agents form covalent bonds with DNA strands, thus preventing cell replication, whereas anticancer antibiotics intercalate into the DNA molecule and this blocks transcription, but also stabilizes the topoisomerase II-DNA complex. Two major clinical issues emerge when considering that various cancer therapies produce these neurotoxicities in a significant number of patients.
|Original language||English (US)|
|Title of host publication||DNA Repair in Cancer Therapy|
|Number of pages||17|
|State||Published - Dec 1 2012|
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