The Re-establishment of Hypersensitive Cells in the Crypts of Irradiated Mouse Intestine

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Abstract
Within 3-6 h of small doses of radiation (.gamma.-rays) the number of dead cells (apoptotic cells) in the crypts of the small intestine reaches peak values. These return to normal levels only after times later than 1 day. After higher doses elevated levels of cell death persist for longer times. The dead cells 1st occur most frequently at the lower positions of the crypt (median value for the distribution of apoptotic fragment is about cell position 6). At later times more dead cells are observed at higher positions. Two doses of radiation separated by various time intervals were used to investigate when after irradiation the cell population susceptible to acute cell death is re-established. Dead cells were scored 3 or 6 h after the 2nd dose. The yield of dead cells after 2 doses represents the sum of the dead cells produced by, and persisting from, 1 dose and new apoptotic cells induced by the 2nd dose. Since the temporal and dose-dependent aspects of the dead-cell yield after the 1st dose alone is known, the additional dead cells attributable to the 2nd dose alone can be determined by subtraction. Within 1-2 days of small doses (0.5 Gy [grays]) the sensitive cells, recognized histologically as apoptotic cells, are reestablished at the base of the crypt (.apprx. cell position 6). After higher doses (9.0 Gy) they are not reestablished until about the 4th day after irradiation. Even in the enlarged regenerating crypsts the sensitive cells are found at the same position at the crypt base. The crypt evidently contains 5 or 6 cells that are susceptible to low doses (0.5 Gy) (hypersensitive cells) and up to a total of only 7 or 8 susceptible cells that can be induced by any dose to enter the sequence of changes implicit in apoptosis. Between 4 and 10 days after an initial irradiation of 9.0 Gy the total number of susceptible cells increased from 7 to 8 to .apprx. 10-13 /crypt.
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