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2015 ; 109
(5
): 399-413
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The Delayed Effects of Acute Radiation Syndrome: Evidence of Long-Term Functional
Changes in the Clonogenic Cells of the Small Intestine
#MMPMID26425901
Booth C
; Tudor GL
; Katz BP
; MacVittie TJ
Health Phys
2015[Nov]; 109
(5
): 399-413
PMID26425901
show ga
Long term or residual damage post-irradiation has been described for many
tissues. In hematopoietic stem cells (HSC), this is only revealed when the HSC
are stressed and required to regenerate and repopulate a myeloablated host. Such
an assay cannot be used to assess the recovery potential of previously irradiated
intestinal stem cells (ISC) due to their incompatibility with transplantation.
The best approximation to the HSC assay is the crypt microcolony assay, also
based on clonogen survival. In the current study, the regenerative capacity of
intestinal clonogenic cells in mice that had survived 13 Gy irradiation (with 5%
bone marrow shielding to allow survival through the hematopoietic syndrome) and
were then aged for 200 d was compared to previously unirradiated age-matched
controls. Interestingly, at 200 d following 13 Gy, there remained a statistically
significant reduction in crypts present in the various small intestinal regions
(illustrating that the gastrointestinal epithelium had not fully recovered
despite the 200-d interval). However, upon re-irradiation on day 196, those mice
previously irradiated had improved crypt survival and regeneration compared to
the age-matched controls. This was evident in all regions of the small intestine
following 11-13 Gy re-exposure. Thus, there were either more clonogens per crypt
within those previously irradiated and/or those that were present were more
radioresistant (possibly because a subpopulation was more quiescent). This is
contrary to the popular belief that previously irradiated animals may have an
impaired/delayed regenerative response and be more radiosensitive.