Rauth A M, Mohindra J K, Tannock I F
Cancer Res. 1983 Sep;43(9):4154-8.
We have observed the selective toxicity of mitomycin C toward hypoxic as compared to aerobic cells in vitro for three established cell lines (Chinese hamster ovary, Chinese hamster V-79, and human HeLa) and for cells from the transplantable KHT murine tumor. The magnitude of the selective toxicity was cell line dependent. We have studied the in vivo effects of mitomycin C against aerobic and hypoxic cells of two transplantable murine tumors: the KHT fibrosarcoma and the 16/C mammary carcinoma. Either mitomycin C was given with radiation to kill most of the aerobic cells, or it was given alone. Endpoints of response were cell survival assessed by lung colony assay for the KHT tumor, and growth delay for the 16/C tumor. In some experiments, mitomycin C appeared more effective when used with radiation than when used alone, but the results of combined treatment fell just within the range of additivity as defined by isobologram analysis. The effects of combined treatment were independent of the order in which drug and radiation were given. Mitomycin C was also used in combination with Adriamycin to treat the 16/C tumor, since we have found previously that Adriamycin spares hypoxic cells in this tumor. In three of four experiments, combined drug effects were slightly greater than predicted by an additive relationship. We conclude that mitomycin C is active against hypoxic cells in two murine tumors, but that it has at most minor specificity for hypoxic as compared to aerobic cells in vivo.
我们已经观察到，与需氧细胞相比，丝裂霉素C在体外对三种已建立的细胞系（中国仓鼠卵巢细胞、中国仓鼠V - 79细胞和人宫颈癌细胞系HeLa）以及可移植的KHT小鼠肿瘤细胞具有选择性毒性。选择性毒性的程度取决于细胞系。我们研究了丝裂霉素C对两种可移植小鼠肿瘤的需氧细胞和缺氧细胞的体内作用：KHT纤维肉瘤和16/C乳腺癌。丝裂霉素C要么与辐射联合使用以杀死大多数需氧细胞，要么单独使用。反应终点为：通过KHT肿瘤的肺集落试验评估细胞存活情况，以及16/C肿瘤的生长延迟情况。在一些实验中，丝裂霉素C与辐射联合使用时似乎比单独使用更有效，但联合治疗的结果仅在等效线分析所定义的相加范围内。联合治疗的效果与给药顺序无关。丝裂霉素C还与阿霉素联合用于治疗16/C肿瘤，因为我们之前发现阿霉素可使该肿瘤中的缺氧细胞免受损伤。在四个实验中的三个实验中，联合用药的效果略大于相加关系所预测的效果。我们得出结论，丝裂霉素C对两种小鼠肿瘤中的缺氧细胞有活性，但与体内的需氧细胞相比，它对缺氧细胞的特异性至多很小。
