Dewhirst M W, Oliver R, Tso C Y, Gustafson C, Secomb T, Gross J F
Duke University Medical Center, Durham, NC 27710.
Int J Radiat Oncol Biol Phys. 1990 Mar;18(3):559-68. doi: 10.1016/0360-3016(90)90061-n.
Viable hypoxic cells have reduced radiosensitivity and could be a potential cause for treatment failure with radiotherapy. The process of reoxygenation, which may occur after radiation exposure, could increase the probability for control. However, incomplete or insufficient reoxygenation may still be a potential cause for local treatment failure. One mechanism that has been thought to be responsible for reoxygenation is an increase in vascular prominence after radiation. However, the effect is known to be heterogeneous. In this study, tumor microvascular hemodynamics and morphologies were studied using the R3230 Ac mammary adenocarcinoma transplanted in a dorsal flap window chamber of the Fischer-344 rat. Measurements were made before and after (at 24 and 72 hr) 5-Gy radiation exposure to assess microvascular changes and to explore possible explanations for the heterogeneity of the effect. There was considerable heterogeneity between tumors prior to radiation. Vascular densities ranged from 67 to 3000 vessels/mm3 and median vessel diameters from 22 to 85 microns. Pretreatment perfusion values varied by a factor of six. In irradiated tumors, conjoint increases in both vascular density and perfusion occurred in most tumors, although the degree of change was variable from one individual to the next. The degree of change in density was inversely related to median pretreatment diameter. Relative change in flow, as predicted by morphometric measurements, overestimated observed changes in flow measured hemodynamically. These results support that heterogeneity in tumor vascular effects from radiation are somewhat dependent on pretreatment morphology as well as relative change in morphology. Since changes in flow could not be completely explained by morphometric measurements, however, it is likely that radiation induced changes in pressure and/or viscosity contribute to the overall effect. Further work in this laboratory will investigate these hypotheses.
存活的缺氧细胞放射敏感性降低，可能是放疗治疗失败的潜在原因。再氧合过程可能在辐射暴露后发生，这可能会增加肿瘤被控制的概率。然而，不完全或不充分的再氧合仍可能是局部治疗失败的潜在原因。一种被认为与再氧合有关的机制是辐射后血管突出增加。然而，已知这种效应是异质性的。在本研究中，使用移植到Fischer-344大鼠背部皮瓣窗口室的R3230 Ac乳腺腺癌研究肿瘤微血管血流动力学和形态。在5 Gy辐射暴露前后（24小时和72小时）进行测量，以评估微血管变化并探索效应异质性的可能解释。辐射前肿瘤之间存在相当大的异质性。血管密度范围为67至3000个血管/mm³，血管中位数直径为22至85微米。预处理灌注值相差6倍。在受照射的肿瘤中，大多数肿瘤的血管密度和灌注都联合增加，尽管个体之间的变化程度各不相同。密度变化程度与预处理中位数直径呈负相关。形态测量预测的血流相对变化高估了血流动力学测量观察到的血流变化。这些结果支持，辐射引起的肿瘤血管效应的异质性在一定程度上取决于预处理形态以及形态的相对变化。然而，由于血流变化不能完全由形态测量解释，辐射引起的压力和/或粘度变化可能对整体效应有贡献。本实验室的进一步工作将研究这些假设。
