Abstract

The effect of dietary copper deficiency on tumour growth, neovascularisation and microvascular integrity was studied in the rat cremaster muscle. Male, weanling Sprague-Dawley rats were fed purified diets which were copper deficient (< 0.5 micrograms g-1 of diet) or copper adequate (5 micrograms g-1 of diet). Seven days after initiation of diets, a chondrosarcoma was implanted in the cremaster muscle of each rat. Five, 10 or 20 days after tumour implantation, rats were anesthetised and their cremasters prepared for observation by intravital microscopy. Intraarterial injection of fluorescein isothiocyanate-conjugated albumin and subsequent observation of fluorescence in the perivascular space indicated no difference in microvascular albumin leakage between the tumour vasculature of copper deficient and copper adequate rats. Neither tumour growth (assessed by wet weight), vascular density (assessed by light microscopy), nor any ultrastructural characteristics of the tumour or its vasculature (assessed by electron microscopy) were affected by copper deficiency. In view of findings by others which indicate changes in tumour characteristics with copper deficiency, we conclude that the copper dependency of tumour growth and vascularisation is a function of the type of tumour, the host tissue, or the conditions of copper depletion.

Highlights

  • Most studies involving the role of copper in angiogenesis have used the rabbit cornea as a model for experimentation

  • Results from experimentation with the cornea demonstrate that tissue copper levels increase prior to angiogenesis (Ziche et al, 1982)

  • Copper was previously shown to complex with fibroblast growth factor (FGF) (Shing, 1988), heparin, and ceruloplasmin (Raju et al, 1984) making these agents angiogenic

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Summary

Introduction

Copper deficiency was shown to inhibit angiogenesis in the rabbit cornea induced by prostaglandin E and BALB/C fibroblasts (Ziche et al, 1982). Brem and co-workers found that a copper deficient diet combined with the copper chelating agent penicillamine inhibited growth of VX2 carcinoma in the brain. Tumours in the rabbit brain remained in an avascular state and failed to develop beyond small nodules. Similar results were observed in the growth and development of rat 9L gliosarcoma (Brem et al, 1990a and b)

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