Abstract

Breast cancer is the first of the most common ten cancers in Iraq. Its etiology is mulifactorial, oxidative stress and lipid peroxidation being suggested to play important roles in carcinogenesis. The purpose of this study was to investigate the oxidant-antioxidant status in breast cancer patients, by measuring SOD isoenzyme activities (total SOD, CuZn-SOD, Mn-SOD and EC-SOD) in plasma and breast tumors, and by estimating thiobarbituric reactive substance (TBRS) in tissue homogenates. General increase in total SOD activity was observed in plasma and tissue samples of breast tumors, greater in the malignant when compared to benign group (p<0.05). Mn- SOD showed a significant decrease in tissue malignant samples (p<0.05), and insignificant decrease in plasma malignant samples compared with control and benign samples. Plasma EC-SOD activity in both patient benign and malignant breast tumors demonstrated 3.5% and 22.8% increase, respectively. However, there was a decrease in tissue EC-SOD activity in malignant breast tumors when compared with benign. A similar tendency was noted for TBRS.We suggested that elevated total SOD might reflect a response to oxidative stress, and then may predict a state of excess reactive oxygen species in the carcinogenesis process. If there is proteolytic removal of the heparin binding domain, EC-SOD will lose its affinity for the extracellular matrix and diffuse out of the tissue. This will result in a decreased EC-SOD activity, thus leading to an increase in the steady-state concentration of O2- in this domain, and increase in EC-SOD activity in extracellular fluid. This might explain the result recorded here concerning the decrease in tissue EC-SOD activity and increase in plasma of breast cancer patients.

Highlights

  • Breast cancer is the first of the commonest ten cancers in Iraq, according to the latest of Iraq Cancer Registry (Alwan, 2010)

  • manganese superoxide dismutase (Mn-SOD) showed a significant decrease in tissue malignant samples (p

  • We suggest that elevated total SOD might reflect a response to oxidative stress, and may predict a state of excess reactive oxygen species in the carcinogenesis process

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Summary

Introduction

Breast cancer is the first of the commonest ten cancers in Iraq, according to the latest of Iraq Cancer Registry (Alwan, 2010). The development of breast cancer is a multifactorial process whose mechanism is still largely unknown. It has been hypothesized that reactive oxygen species (ROS) and oxidative stress may play a critical role in breast cancer etiology and progression and be associated with the proliferation potencies of breast cancer cells (Brown & Bicknell, 2001; Mobley & Brueggemeier, 2004; Xing et al, 2008). Reactive oxygen is related to both the arrest of the growth and the start of cell differentiation. Low concentrations of reactive oxygen intermediates may be beneficial, or even indispensable in processes such as intracellular messaging and defense against microorganisms, but higher amount of active oxygen may be harmful to cells and organisms (Dean et al, 1997; Buettner, 2011). Oxidative damage to critical biomolecules (i.e. ,DNA ,RNA ,proteins and lipids) accumulates and eventually disrupts normal metabolism, resulting in a wide variety of biological effects ranging from alterations in signal transduction and gene expression (Demple, 1991; Guyton et al.,1996; Monteiro & Stem, 1996; Sun & Oberley, 1996) to mitogenesis (Budroe et al, 1992), transformation (Ames, 1983; Cerutti, 1985; Cerutti et al, 1989), mutagenesis (Shay & Werbin, 1989; Moraes et al, 1990) and cell death (Spitz et al, 1990; Spitz et al, 1992; Sullivan et al.,1992)

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