Department of Radiation Oncology, Beaumont Health, Royal Oak, MI, U.S.A.
Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, U.S.A.
In Vivo. 2019 Nov-Dec;33(6):1757-1766. doi: 10.21873/invivo.11666.
BACKGROUND/AIM: We tested JP4-039, a GS-nitroxide radiation damage mitigator in proton therapy of Fanconi anemia (FA) mice.
Fanca and Fanca bone marrow stromal cells were pre-treated with JP4-039 and irradiated with either protons or photons (0-10 GyRBE) followed by clonogenic survival and β-Galactosidase senescence analysis. Fanca and Fanca mice were pretreated with JP4-039 for 10 min prior to oropharyngeal irradiation with either protons or photons (0 or 30 GyRBE) followed by sacrifice and measurement of oral cavity ulceration, distant hematopoietic suppression, and real-time polymerase chain reaction analysis.
JP4-039 reduced oral cavity ulceration in Fanca mice, transcripts Nfkb, Ap1, Sp1, and Nrf2, and proton therapy induced distant marrow suppression.
JP4-039 protected Fanca and Fanca cells and mouse oral cavity from both proton and photon radiation.
背景/目的:我们测试了 JP4-039,一种用于范可尼贫血(FA)小鼠质子治疗的 GS-氮氧自由基辐射损伤缓解剂。
Fanca 和 Fanca 骨髓基质细胞用 JP4-039 预处理,然后用质子或光子(0-10 GyRBE)照射,随后进行集落形成存活和β-半乳糖苷酶衰老分析。Fanca 和 Fanca 小鼠在接受质子或光子(0 或 30 GyRBE)口腔照射前用 JP4-039 预处理 10 分钟,然后处死并测量口腔溃疡、远处造血抑制和实时聚合酶链反应分析。
JP4-039 减少了 Fanca 小鼠的口腔溃疡,降低了 Nfkb、Ap1、Sp1 和 Nrf2 的转录本,并诱导了质子治疗引起的远处骨髓抑制。
JP4-039 保护了 Fanca 和 Fanca 细胞以及小鼠口腔免受质子和光子辐射的损伤。