A Quantitative Morphological Analysis of the Response of a Transplantable Rat Fibrosarcoma to Cyclophosphamide

The response of a transplantable rat fibrosarcoma, RIB(5), to a single injection of 100 mg/kg body weight of cyclophosphamide, 0·5, 1, 2 and 3 days after treatment, has been studied by means of a morphometric analysis of tumour sections and has been compared to the changes occurring in untreated tumours. The results showed a transitory increase in thymidine labelling index 12 hours after drug injection accompanied by a low mitotic index which persisted for a further 12 hours. These observations are compared with, and confirm, a previous study involving analysis of smear preparations from tumour cell suspensions. The changes in the proportion of the tumour occupied by erythrocytes and necrotic elements are described. The results of the morphometric analysis have shown the changes occurring in the outer, intermediate and inner zones of the tumour. In all control tumours, and tumours up to 2 days after cyclophosphamide treatment, necrosis was predominant in the inner zone and tumour cell proliferation was most marked in the outer zone. In contrast, 3 days after cyclophosphamide treatment proliferation was predominant in the inner zone and the amount of necrosis was approximately the same in each zone.