%0 Journal Article
%T Hypoxia and oxidative stress in breast cancer: Oxidative stress - its effects on the growth, metastatic potential and response to therapy of breast cancer
%A Nicholas S Brown
%A Roy Bicknell
%J Breast Cancer Research
%D 2001
%I BioMed Central
%R 10.1186/bcr315
%X Oxygen radicals are continuously generated within mammalian cells, this being a consequence of the use of oxygen in aerobic respiration. Superoxide is generated within the mitochondria and is sequentially reduced to hydrogen peroxide and hydroxyl radicals. These species damage DNA, producing the mutations that initiate tumours and sustain progression [1]. Epidemiological studies suggest that a diet that is rich in antioxidants may help to prevent the development of breast carcinoma; this evidence contributed to recent UK Government advice that individuals should consume at least five portions of fruit or vegetables each day. The UK Department of Health has now translated this recommendation into initiatives such as the National School Fruit Scheme and the Five-a-day Community Projects (www.doh.gov.uk). The role of ROS in breast carcinoma may not be limited to early mutagenic events, however. Carcinoma cells are frequently under persistent oxidative stress. Human tumour cell lines in vitro produce ROS at a far greater rate than do non-transformed cell lines [2], and markers of constitutive oxidative stress have been detected in samples from in vivo breast carcinomas [3,4]. 8-Hydroxy-2'-deoxyguanosine, one of the major oxidatively modified DNA base products, is almost 10 times more prevalent in invasive ductal breast carcinoma cells than in normal control samples from the same patient [3]. It appears unlikely that such a high level of oxidatively modified DNA is exclusively due to the mutagens that initiated the tumour. Persistent oxidative stress within carcinoma cells may instead be responsible for the accumulation of 8-hydroxy-2'-deoxyguanosine.Oxygen radicals are not only generated in the mitochondria. Neutrophils and macrophages produce ROS via a plasma membrane bound nicotinamide adenine dinucleotide phosphate, reduced form (NADPH)-oxidase. The radicals are generated for cell killing and bactericidal activities. The NADPH-oxidase is not exclusive to these cells,
%K angiogenesis
%K apoptosis
%K breast cancer
%K metastasis
%K oxidative stress
%U http://breast-cancer-research.com/content/3/5/323