Oncology 401_2013

Repair of cellular damage reoxygenation of the tumor

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Unformatted text preview: ation Therapy in a Nutshell Radiation Therapy in a Nutshell Radiation Therapy in a Nutshell ¡༊  Electrons directly damage biologic molecules (Direct Effect) §༊  Accounts for <30% of damage ¡༊  Electrons generate free radicals, which cause damage (Indirect Effect) §༊  Accounts for >70% of damage ¡༊  DNA = target of radiation injury ¡༊  Principal lethal injury to DNA is the double strand DNA break §༊  Single strand breaks can be repaired, and are “sub- lethal” §༊  Double strand breaks cannot be repaired, and are lethal Radiation Damage of DNA Consequences for the cell: repair mis-repair not repaired mutation viable cell cancer cell death 6 hours 6 hours ¡༊  Repair of cellular damage ¡༊  Reoxygenation of the tumor ¡༊  Redistribution within the cell cycle ¡༊  Repopulation of cells —༉  Irradiation of cells in culture —༉  Measure survival of cells after various doses of radiation —༉  Cells die exponentially after radiation —༉  Cell Survival Curve = plot of their survival vs dose ¡༊  Plotting survival on a log scale against single dose exposure is almost a straight line ¡༊  The curve implies the magnitude of killing varies by the size of the single dose of radiation ¡༊  When a single dose is divided into 2 smaller doses separated by time, there is less proportional cell killing ¡༊  This sparing with fractionation is a result of Sublethal Damage Repair ▪  The bend in a cell survival curve is the graphical representation of sublethal damage repair ▪  A cell with no sublethal repair will manifest as a straight line ¡༊  Dividing cell populations are more radio- sensitive §༊  more of the cells are in G2- M, and thus unable to muster sublethal damage repair….. ¡༊  Sublethal damage repair is rapid in normal tissues, with a half- life of 30- 45 minutes. §༊  Most repair is complete after 6 hours §༊  Many small fractions at minimum intervals of 6 hours: normal...
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