Endothelial proliferation in tumours and normal tissues: continuous labelling studies.

The proliferation rate of vascular endothelium has been studied using repeated administrations of tritiated thymidine, given every 8 h for 1 week. Five experimental mouse tumours have been investigated and compared with placenta and with normal tissues. The large difference in labelling indices between tumour and normal endothelium that has previously been detected with single injections of ([3H]dT) is confirmed by these continuous labelling studies. The potential doubling time of the tumour endothelium is estimated to be between 2.4 and 13 days for the five tumours. Tpot for the placenta is at least as short. The turnover time of the normal tissue endothelium is estimated to be 20-2000 times longer (47-23,000 days) and does not seem to differ in slow turnover tissues e.g. lung and liver from that in tissues where the parenchymal cells are rapidly turning over e.g. jejunum or skin

Endothelial-cell proliferation in experimental tumours.

The proliferation characteristics of vascular endothelium have been studied in 131 individual experimental tumours, representing 18 transplanted tumour lines. The labelling index (LI) is high in most tumours, with a mean value of 0.9%, regardless of the growth rate of the tumours, or whether different tumour types are considered or individual tumours from within one line are studied in detail. A similar high LI value has been found by others for a human tumour. These high LI values may even underestimate the proliferation in new capillary buds. The high proliferative index of tumour endothelium is in marked contrast with the previously reported low 3HTdR uptake into normal tissue blood vessels. It seems likely that it is the type of new vessels formed that will influence tumour growth rates more than the simple rate of endothelial-cell proliferation. The large difference between the proliferation characteristics of tumour endothelium and normal tissue endothelium, recently identified as a possible approach for tumour therapy, has now been confirmed for a range of animal tumours and a human tumour