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The number of clonogenic cells per intestinal crypt has been estimated in control and gamma-irradiated mice, from the response to a single or two test doses. Control unirradiated mice contained 43 +/- 8 clonogenic cells per crypt, which was reduced to about 3 per crypt immediately after 8.0 Gy. After a mitotic delay which was approximately 18 h or 2.25 h/Gy the number of clonogenic cells per crypt increased exponentially with a doubling time of 21 +/- 4 h to reach the control values by about the 4th day postirradiation. The growth curve was related to the changes in total cellularity and the cell production rate per crypt. Since both of these rise during the period of clonogenic regrowth some clonogenic cells must be diverted into the dividing transit cell population, so that the cell cycle time will be shorter than the doubling time given above.

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In this study the manifestation of DNA damage at the nucleoid level was examined in several AT cell lines using an image analysis system to directly visualize and measure the changes in DNA loop size which occur when increasing concentrations of propidium iodide (PI) are used to titrate the DNA supercoiling response (the 'fluorescent halo assay'). This response consists of a relaxation (0.5-7.5 micrograms/ml PI) and rewinding phase (10-50 micrograms/ml PI), the latter of which is impaired by the presence of DNA strand breaks in irradiated cells. In addition to the inhibition of DNA rewinding seen immediately after irradiation at 0 degrees C, the supercoiling response of AT diploid fibroblasts indicated an increased amount of DNA unwinding compared to fibroblasts from unaffected individuals. This difference appeared to saturate, since the excess in DNA loop size over that seen in irradiated fibroblasts from unaffected individuals remained constant after 5 Gy. These results may reflect a greater instability of the DNA-nuclear matrix attachment points in irradiated AT fibroblasts. The DNA supercoiling response in irradiated transformed AT fibroblasts and AT lymphoblasts did not differ from that observed in unaffected cells of the same type. However, all of the immortalized cell lines (AT and unaffected) had inherently larger DNA loop sizes than diploid fibroblasts and exhibited excess unwinding after irradiation.

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