Abstract：
:Tissue survival responses to ionizing radiation are nonlinear with dose, rather yielding tissue-specific descending curves that impede straightforward analysis of biologic effects. Apoptotic cell death often occurs at low doses, while at clinically relevant intermediate doses, double-strand break misrepair yields mitotic death that determines outcome. As researchers frequently use a single low dose for experimentation, such strategies may inaccurately depict inherent tissue responses. Cutting edge radiobiology has adopted full dose survival profiling and devised mathematical algorithms to fit curves to observed data to generate highly reproducible numerical data that accurately define clinically relevant inherent radiosensitivities. Here, we established a protocol for irradiating organoids that delivers radiation profiles simulating the organ of origin. This technique yielded highly similar dose-survival curves of small and large intestinal crypts in vivo and their cognate organoids analyzed by the single-hit multi-target (SHMT) algorithm, outcomes reflecting the inherent radiation profile of their respective Lgr5+ stem cell populations. As this technological advance is quantitative, it will be useful for accurate evaluation of intestinal (patho)physiology and drug screening. SIGNIFICANCE: These findings establish standards for irradiating organoids that deliver radiation profiles that phenocopy the organ of origin.See related commentary by Muschel et al., p. 927.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Martin ML,Adileh M,Hsu KS,Hua G,Lee SG,Li C,Fuller JD,Rotolo JA,Bodo S,Klingler S,Haimovitz-Friedman A,Deasy JO,Fuks Z,Paty PB,Kolesnick RNdoi
10.1158/0008-5472.CAN-19-0312subject
Has Abstractpub_date
2020-03-01 00:00:00pages
1219-1227issue
5eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-19-0312journal_volume
80pub_type
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