Abstract

An oestrogen-sensitive rat mammary tumour (OES HR1) has been grown in normal female rats and in female and male rats supplemented with oestrone. In some rats, after the tumour was established, both exogenous and endogenous sources of oestrogen were removed--a treatment which inhibited further growth of the tumour. The proliferative characteristics of the tumours were measured by injecting the rats with deoxybromouridine (BrdU) 4 h before removing the tumour. Extracted nuclei were reacted with anti-BrdU and the labelling index and DNA content measured by flow cytometry. A correlation between the number of (diploid) host cells present and the number of (aneuploid) tumour cells in S-phase of the cell cycle was observed. This result suggests that there are paracrine interactions between tumour and host cells. We also observed that, on oestrogen ablation, the labelling index was significantly reduced while the percentage of cells in S-phase changed far less. The demonstration that there are cells in S-phase which are not proliferating highlights a possible problem with the measurement of proliferation in human tumours from a DNA histogram.

Highlights

  • We have been studying the proliferative behaviour of an oestrogen-sensitive rat tumour using labelling with bromodeoxyuridine (BrdU) and flow cytometry (Smith et al, 1991)

  • In this paper we report a correlation between the labelling index of the tumour and the number of host cell nuclei

  • The results suggest that, in the absence of growth stimuli, cells can stop proliferating in S-phase of the cell cycle

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Summary

Introduction

We have been studying the proliferative behaviour of an oestrogen-sensitive rat tumour using labelling with bromodeoxyuridine (BrdU) and flow cytometry (Smith et al, 1991). This system has the advantage that the growth rate of the tumour can be manipulated by altering the level of oestrogen in the animal. Because normal (diploid) can be distinguished from tumour (aneuploid) nuclei in a DNA histogram, the labelling index can be measured and the percentage of host nuclei can be quantified in the same experiment This tumour offers a good model for the study of stromal influences on tumour growth in vivo

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