Rockwell S, Moulder J E
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06510.
Int J Radiat Oncol Biol Phys. 1990 Jul;19(1):197-202. doi: 10.1016/0360-3016(90)90154-c.
Transplanted tumors in rats and mice have been used extensively in radiobiology studies examining the biological basis and therapeutic implications of hypoxia in solid tumors, and in studies evaluating new agents and regimens which may circumvent the radioprotective effects of hypoxic cells. This use of rodent tumors assumes that data obtained using rapidly-growing transplanted tumors arising in inbred rodents can be extrapolated meaningfully to the treatment of primary and/or metastatic lesions in heterozygous humans. The studies reported here examine one facet of this critical assumption by comparing the hypoxic fractions of transplanted rodent tumors with those of human tumor cell lines xenografted into immune deficient mice. No significant differences were found between the hypoxic fractions of the xenografts and those of mouse tumors. This finding eliminates several possible bases for predicting that the oxygenation of human tumors might be systematically different from that of the rodent tumors often used in preclinical radiobiology studies, and supports the hypothesis that human tumors contain hypoxic cells which may be critical in determining their response to therapy.
大鼠和小鼠的移植肿瘤已广泛应用于放射生物学研究,以检验实体瘤缺氧的生物学基础和治疗意义,以及评估可能规避缺氧细胞放射保护作用的新药物和治疗方案。使用啮齿动物肿瘤进行此类研究的前提是,利用近交系啮齿动物体内快速生长的移植肿瘤所获得的数据能够有意义地外推至杂合子人类原发性和/或转移性病变的治疗。本文所报告的研究通过比较移植的啮齿动物肿瘤与移植到免疫缺陷小鼠体内的人类肿瘤细胞系的缺氧分数,检验了这一关键假设的一个方面。异种移植瘤与小鼠肿瘤的缺氧分数之间未发现显著差异。这一发现排除了几个可能预测人类肿瘤氧合与临床前放射生物学研究中常用的啮齿动物肿瘤存在系统性差异的依据,并支持了以下假设:人类肿瘤含有缺氧细胞,这些细胞可能对确定其治疗反应至关重要。