Guichard M, Lespinasse F, Trotter M, Durand R, Chaplin D
Laboratoire de Radiobiologie Cellulaire (Unité Inserm 247), Institut Gustave-Roussy, Villejuif, France.
Radiother Oncol. 1991 Feb;20(2):117-23. doi: 10.1016/0167-8140(91)90145-7.
The effect of post-irradiation hypoxia induced by 5 or 30 mg/kg hydralazine has been studied in three human tumour xenografts (two rectocolic adenocarcinomas and one melanoma) treated with two doses of misonidazole similar to those used in patients (0.1 and 0.2 mg/g). Only a small sensitization was detected using an in vitro colony assay. These results are in marked contrast to the results obtained with rodent tumours. This difference between human tumour xenografts and rodent tumours might be explained by differences in the reduction of tumour blood flow after hydralazine administration (5 and/or 10 mg/kg). Using the laser Doppler technique, the tumour blood flow reduction was 33% and 25% of the control for NA11 and HRT18 tumours, respectively. In contrast, hydralazine induced a 60-70% reduction in blood flow in the murine SCCVII tumour. Using the fluorescent marker Hoechst 33342, the reduction in perfusion was again more pronounced in the murine tumour as compared to the Na11 and HRT18 xenografts. The differences between human tumour xenografts and rodent tumours are not linked to the mouse strain used (nude versus C3H) nor to a tumour bed effect.
已在三种人肿瘤异种移植模型（两种直肠结肠癌和一种黑色素瘤）中研究了5或30mg/kg肼苯哒嗪诱导的照射后缺氧的影响，这些模型用了两剂与患者所用剂量相似的米索硝唑（0.1和0.2mg/g）进行治疗。使用体外集落测定法仅检测到了轻微的增敏作用。这些结果与用啮齿动物肿瘤获得的结果形成了显著对比。人肿瘤异种移植模型与啮齿动物肿瘤之间的这种差异可能是由于给予肼苯哒嗪（5和/或10mg/kg）后肿瘤血流减少的差异所致。使用激光多普勒技术，NA11和HRT18肿瘤的肿瘤血流减少分别为对照的33%和25%。相比之下，肼苯哒嗪使小鼠SCCVII肿瘤的血流减少了60 - 70%。使用荧光标记物Hoechst 33342，与Na11和HRT18异种移植模型相比，小鼠肿瘤中的灌注减少再次更为明显。人肿瘤异种移植模型与啮齿动物肿瘤之间的差异与所用的小鼠品系（裸鼠与C3H）无关，也与肿瘤床效应无关。
