Abstract
Bone marrow suppression due to exposure to ionizing radiation is a significant clinical problem associated with radiation therapy as well as with nonmedical radiation exposure. Currently, there are no small molecule agents available that can enhance hematopoietic regeneration after radiation exposure. Here, we report on the effective mitigation of acute hematopoietic radiation syndrome in mice by the synthetic triterpenoid, RTA 408. The administration of a brief course of RTA 408 treatment, beginning 24 h after lethal doses of radiation to bone marrow, significantly increased overall survival. Importantly, treatment with RTA 408 led to the full recovery of steady state hematopoiesis with normalization of the frequency of hematopoietic stem and progenitor cells. Moreover, hematopoietic stem cells from RTA 408-mitigated mice showed lineage-balanced, long-term, multilineage potential in serial transplantation assays, indicative of their normal self-renewal activity. The potency of RTA 408 in mitigating radiation-induced bone marrow suppression makes it an attractive candidate for potential clinical use in treating both therapy-related and unanticipated radiation exposure.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 338-344 |
| Number of pages | 7 |
| Journal | Radiation Research |
| Volume | 183 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2015 |
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ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging
- Biophysics
- Radiation
- Medicine(all)
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The triterpenoid RTA 408 is a robust mitigator of hematopoietic acute radiation syndrome in mice. / Goldman, Devorah; Alexeev, Vitali; Lash, Elizabeth; Guha, Chandan; Rodeck, Ulrich; Fleming, William.
In: Radiation Research, Vol. 183, No. 3, 01.03.2015, p. 338-344.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The triterpenoid RTA 408 is a robust mitigator of hematopoietic acute radiation syndrome in mice
AU - Goldman, Devorah
AU - Alexeev, Vitali
AU - Lash, Elizabeth
AU - Guha, Chandan
AU - Rodeck, Ulrich
AU - Fleming, William
PY - 2015/3/1
Y1 - 2015/3/1
N2 - Bone marrow suppression due to exposure to ionizing radiation is a significant clinical problem associated with radiation therapy as well as with nonmedical radiation exposure. Currently, there are no small molecule agents available that can enhance hematopoietic regeneration after radiation exposure. Here, we report on the effective mitigation of acute hematopoietic radiation syndrome in mice by the synthetic triterpenoid, RTA 408. The administration of a brief course of RTA 408 treatment, beginning 24 h after lethal doses of radiation to bone marrow, significantly increased overall survival. Importantly, treatment with RTA 408 led to the full recovery of steady state hematopoiesis with normalization of the frequency of hematopoietic stem and progenitor cells. Moreover, hematopoietic stem cells from RTA 408-mitigated mice showed lineage-balanced, long-term, multilineage potential in serial transplantation assays, indicative of their normal self-renewal activity. The potency of RTA 408 in mitigating radiation-induced bone marrow suppression makes it an attractive candidate for potential clinical use in treating both therapy-related and unanticipated radiation exposure.
AB - Bone marrow suppression due to exposure to ionizing radiation is a significant clinical problem associated with radiation therapy as well as with nonmedical radiation exposure. Currently, there are no small molecule agents available that can enhance hematopoietic regeneration after radiation exposure. Here, we report on the effective mitigation of acute hematopoietic radiation syndrome in mice by the synthetic triterpenoid, RTA 408. The administration of a brief course of RTA 408 treatment, beginning 24 h after lethal doses of radiation to bone marrow, significantly increased overall survival. Importantly, treatment with RTA 408 led to the full recovery of steady state hematopoiesis with normalization of the frequency of hematopoietic stem and progenitor cells. Moreover, hematopoietic stem cells from RTA 408-mitigated mice showed lineage-balanced, long-term, multilineage potential in serial transplantation assays, indicative of their normal self-renewal activity. The potency of RTA 408 in mitigating radiation-induced bone marrow suppression makes it an attractive candidate for potential clinical use in treating both therapy-related and unanticipated radiation exposure.
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U2 - 10.1667/RR13900.1
DO - 10.1667/RR13900.1
M3 - Article
C2 - 25738896
AN - SCOPUS:84925068204
VL - 183
SP - 338
EP - 344
JO - Radiation Research
JF - Radiation Research
SN - 0033-7587
IS - 3
ER -