Free radicals, metals and antioxidants in oxidative stress-induced cancer

For a long time, superoxide generation by an NADPH oxidase was considered as an oddity only found in professional phagocytes. Over the last years, six homologs of the cytochrome subunit of the phag...

/pdf/the-nox-family-of-ros-generating-nadph-oxidases-physiology-zjc88zvh59.pdf

The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

Oxidative mechanisms in the toxicity of metal ions

Oxidative Stress, Inflammation, and Cancer: How Are They Linked?

Sixteen years have passed since the description of the nuclear factor-кB (NF-кB) as a regulator of к light-chain gene expression in murine B lymphocytes (Sen & Baltimore, 1986a) During that time, over 4,000 publications have appeared, characterizing the family of Rel/NF-кB transcription factors involved in the control of a large number of normal and pathological cellular processes The physiological functions of NF-кB proteins include immunological and inflammatory responses, developmental processes, cellular growth and modulating effects on apoptosis In addition, these factors are activated in a number of diseases, including cancer, arthritis, acute and chronic inflammatory states, asthma, as well as neurodegenerative and heart diseases

Activators and target genes of Rel/NF-kappaB transcription factors.

Alterations of oxidative phosphorylation in tumour cells were originally believed to have a causative role in cancerous growth1. More recently, mitochondria have again received attention with regards to neoplasia, largely because of their role in apoptosis and other aspects of tumour biology2,3,4,5,6,7,8. The mitochondrial genome is particularly susceptible to mutations because of the high level of reactive oxygen species (ROS) generation in this organelle, coupled with a low level of DNA repair9,10,11,12. However, no detailed analysis of mitochondrial DNA in human tumours has yet been reported. In this study, we analysed the complete mtDNA genome of ten human colorectal cancer cell lines by sequencing and found mutations in seven (70%). The majority of mutations were transitions at purines, consistent with an ROS-related derivation. The mutations were somatic, and those evaluated occurred in the primary tumour from which the cell line was derived. Most of the mutations were homoplasmic, indicating that the mutant genome was dominant at the intracellular and intercellular levels. We showed that mitochondria can rapidly become homogeneous in colorectal cancer cells using cell fusions. These findings provide the first examples of homoplasmic mutations in the mtDNA of tumour cells and have potential implications for the abnormal metabolic and apoptotic processes in cancer.

Somatic mutations of the mitochondrial genome in human colorectal tumours

Validation of Lucigenin (Bis-N-methylacridinium) as a Chemilumigenic Probe for Detecting Superoxide Anion Radical Production by Enzymatic and Cellular Systems*

Michael A. Trush

Papers

Somatic mutations of the mitochondrial genome in human colorectal tumours

Validation of Lucigenin (Bis-N-methylacridinium) as a Chemilumigenic Probe for Detecting Superoxide Anion Radical Production by Enzymatic and Cellular Systems*

Diphenyleneiodonium, an NAD(P)H oxidase inhibitor, also potently inhibits mitochondrial reactive oxygen species production.

An overview of the relationship between oxidative stress and chemical carcinogenesis.

Mitochondrial adaptations to obesity-related oxidant stress.