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1. Cell Survival Curves Reproductive Integrity

2. REPRODUCTIVE INTEGRITY A cell survival curve describes the relationship between the radiation dose and the proportion of cells that survive. What is meant by “survival”? Cell survival, or its converse, cell death, may mean different things in different contexts; therefore, a precise defi nition is essential. For differentiated cells that do not proliferate, such

3. as nerve, muscle, or secretory cells, death can be defi ned as the loss of a specifi c function. For proliferating cells, such as stem cells in the hematopoietic system or the intestinal epithelium, loss of the capacity for sustained proliferation— that is, loss of reproductive integrity —is an appropriate defi nition . This is sometimes called reproductive death . This is certainly the end point measured with cells cultured in vitro . This defi nition refl ects a narrow view of

4. radiobiology. A cell may still be physically present and apparently intact, may be able to make proteins or synthesize DNA, and may even be able to struggle through one or two mitoses; but if it has lost the capacity to divide indefi nitely and produce a large number of progeny, it is by defi nition dead; it has not survived. A survivor that has retained its reproductive integrity and is able to proliferate indefi nitely to produce a large clone or colony is said to be clonogenic .

5. This defi nition is generally relevant to the radiobiology of whole animals and plants and their tissues. It has particular relevance to the radiotherapy of tumors. For a tumor to be eradicated, it is only necessary that cells be “killed” in the sense that they are rendered unable to divide and cause further growth and spread of the malignancy. Cells may die by different mechanisms,

6. as is described here subsequently. For most cells, death while attempting to divide, that is, mitotic death , is the dominant mechanism following irradiation. For some cells, programmed cell death, or apoptosis , is important. Whatever the mechanism, the outcome is the same: The cell loses its ability to proliferate indefi nitely , that is, its reproductive integrity.