Reactive oxygen species and antioxidant mechanisms in human tissues and their relation to malignancies

Abstract

Reactive oxygen species (ROS) are formed in mammalian cells as a consequence of aerobic respiration. Despite multiple conserved redox modulating systems, a given proportion of ROS continuously escape from the mitochondrial respiratory chain, being sufficiently potent to damage cells in various ways, including numerous carcinogenic DNA mutations. Oxidative stress resulting from an imbalanced ratio between ROS production and detoxification may also disturb physiological signal transduction, lead to chain reactions in lipid layers, and damage DNA repair enzymes. The significance of ROS and antioxidant systems in carcinogenesis is still complicated and in many ways contradictory. Enhanced antioxidant mechanisms in tumor cells in vivo have been implicated in chemoresistance and lead to poor prognosis, whereas most in vitro studies have reported tumor-suppressing properties of antioxidant enzymes. The present review aims to clarify the significance of oxidative stress and the role of cell redox state modulating systems in human malignancies in light of the current literature.

8-Hydroxydeoxyguanosine: a new potential independent prognostic factor in breast cancer

“…8-OxodG is one of the most widely used biomarkers of oxidative stress, mainly because of its abundance in DNA and also (Karihtala and Soini, 2007). Compared with other bases, guanine most readily undergoes an oxidative attack in the presence of ROS (Peoples and Karnes, 2005).…”

“…These reactions in connection with oncogenes or tumour suppressor genes may result in the initiation of cancer (Loft and Poulsen, 1996). Several recent studies have shown high ROS levels in carcinoma cells compared with the surrounding healthy tissue (reviewed in Karihtala and Soini, 2007). Under normal conditions, ROS are maintained within narrow boundaries by scavenging systems, such as superoxide dismutases, peroxiredoxins (Prx) and glutathione-related antioxidant defences.…”

Explaining sex difference in cancer risk: Might it be related to excess iron?

“…The formation of ROS and especially hydroxyl radical leads to reactions with DNA, proteins and lipids inducing mutations and cellular damage. 5,6 As a consequence of these reactions, high levels of iron have been identified as a risk factor for the development of cancer. 7,8 Several pathways for iron-induced carcinogenesis have been proposed.…”

Clear cell carcinoma of the ovary: Potential pathogenic mechanisms (Review)

“…The representative antioxidant proteins identified in the cEOC include glutathione S-transferases, peroxidases, and superoxide dismutases, and activation of protective genes, including those encoding the heat shock proteins (8,12,13,22). On the contrary, enhanced antioxidant mechanisms have been implicated in chemoresistance and lead to poor prognosis (23). ROS effects can be silenced by high concentrations of antioxidants, whereas in some cells with damaged mitochondria, the opposite effect is possible (24).…”