与外部低剂量率γ射线照射相比，67镓衰变在HL60细胞中的生物学效应：对增殖、G2期阻滞和克隆形成能力的影响。

Biological effectiveness of 67-gallium decay in HL60 cells compared with external low dose rate gamma irradiation: effects on proliferation, G2 arrest, and clonogenic capacity.

作者信息

Jonkhoff A R, von Dieren E B, Huijgens P C, Versteegh R T, Dräger A, vd Loosdrecht A A, Teule G J

出版信息

Int J Radiat Oncol Biol Phys. 1994 Aug 30;30(1):117-24. doi: 10.1016/0360-3016(94)90526-6.

DOI:10.1016/0360-3016(94)90526-6

PMID:8083104

Abstract

PURPOSE

Estimation of the relative biological effectiveness of electron emissions of 67Gallium for cell growth delay and inactivation.

METHODS AND MATERIALS

Human myeloid HL60 cells were incubated in vitro with 0.74 MBq/mL, 1.48 MBq/mL, or 2.96 MBq/mL of 67Gallium for 4 days. Proliferation (vital cell counts and colorimetric tetrazolium assay), clonogenic survival, and cell-cycle effects were compared with responses of HL60 cells externally irradiated with 0.78, 10.37, and 13.22 Gy by an external 67Gallium source. Dosimetric calculations were performed by Monte Carlo simulations (10,000 events).

RESULTS

Proliferation of cells was equally inhibited after 67Gallium incubation with 1.48 and 2.96 MBq/mL compared with 10.37 and 13.22 Gy external irradiation. Irradiation with 10.37 and 13.22 Gy caused a 81% and 89% reduction of Colony Forming Units, compared with 34%, 66%, and 80% reduction after 67Gallium incubation with 0.74, 1.48, and 2.96 MBq/mL, respectively. Peak values for G2/M accumulation were reached on day 4 for the cells externally irradiated with 10.37 and 13.22 Gy (47.5% and 56.7%) and on day 5 after 67Gallium incubation with 0.74 MBq/mL, 1.48 MBq/mL, and 2.96 MBq/mL (26.7%, 43.4%, and 58.2%).

CONCLUSIONS

67Gallium incubation exerts a significant cytotoxic effect on human HL60 cells, which, on the basis of dosimetric studies, may be mainly ascribed to conversion electrons (80 KeV) and 8 KeV Auger electrons. Low energy (< 1 keV) Auger electrons do not contribute significantly. The relative biological effectiveness of 67Gallium compared with external low dose rate gamma irradiation is about 1.0 for clonogenic survival and approximately 1.8 and 1.5 for proliferation inhibition and G2 arrest, respectively. For in vivo therapy, this might implicate that higher doses of 67Gallium than 131Iodine or 90Yttrium are necessary for the same biological effect.

摘要

目的

评估67镓电子发射对细胞生长延迟和失活的相对生物效应。

方法和材料

将人髓系HL60细胞在体外分别与0.74 MBq/mL、1.48 MBq/mL或2.96 MBq/mL的67镓孵育4天。将增殖情况（活细胞计数和比色四氮唑测定）、克隆形成存活率和细胞周期效应与用外部67镓源以0.78、10.37和13.22 Gy进行外部照射的HL60细胞的反应进行比较。通过蒙特卡罗模拟（10,000次事件）进行剂量学计算。

结果

与10.37和13.22 Gy的外部照射相比，67镓以1.48和2.96 MBq/mL孵育后，细胞增殖受到同等程度的抑制。10.37和13.22 Gy的照射导致集落形成单位分别减少81%和89%，而67镓以0.74、1.48和2.96 MBq/mL孵育后，集落形成单位分别减少34%、66%和80%。用10.37和13.22 Gy进行外部照射的细胞在第4天达到G2/M积累的峰值（分别为47.5%和56.7%），而用0.74 MBq/mL、1.48 MBq/mL和2.96 MBq/mL的67镓孵育的细胞在第5天达到峰值（分别为26.7%、43.4%和58.2%）。

结论

67镓孵育对人HL60细胞具有显著的细胞毒性作用，根据剂量学研究，这可能主要归因于转换电子（80 KeV）和8 KeV俄歇电子。低能量（<1 keV）俄歇电子的贡献不显著。与外部低剂量率γ射线照射相比，67镓对克隆形成存活的相对生物效应约为1.0，对增殖抑制和G2期阻滞的相对生物效应分别约为1.8和1.5。对于体内治疗，这可能意味着对于相同的生物学效应，需要比131碘或90钇更高剂量的67镓。