Figure 1.

Oxygen radicals and oxygen insufficiency (hypoxia) co-operatively promote tumour angiogenesis. Breast carcinomas frequently outgrow their blood supply, leading to oxygen insufficiency (hypoxia) within the tumour. Hypoxia causes necrosis, and DNA is subsequently degraded to its constituent bases. Any thymidine released is catabolized by thymidine phosphorylase, an enzyme that is frequently overexpressed within breast carcinomas. Thymidine phosphorylase activity causes oxygen radical production, as described by Brown et al [6]. Reoxygenation of the tumour after hypoxia will drive additional oxygen radical formation. Breast tumours are also oxidatively stressed by nonhypoxic mechanisms, such as glucose deprivation, metabolic alterations and macrophage infiltration. Hypoxia causes the accumulation of the transcription factor HIF-1, which promotes transcription of the angiogenic factor VEGF. HIF-1 levels may also be increased by oxygen radicals. In addition, oxygen radicals increase production of the angiogenic factors VEGF and IL-8 via HIF-1-independent mechanisms.