Increased oxidative DNA damage and impaired antioxidant defense system in patients with gastrointestinal cancer

doi:10.1016/j.ejim.2012.02.001

European Journal of Internal Medicine

Volume 23, Issue 4, June 2012, Pages 350-354

https://doi.org/10.1016/j.ejim.2012.02.001 Get rights and content

Abstract

Background

Highly active intermediates are formed in aerobic metabolism which in turn leads to cellular damage. It is increasingly proposed that free radicals play a key role in human cancer development. The aim of this study was to investigate changes in 8-hydroxy-deoxyguanosine, nitrite + nitrate, total glutathione, total antioxidant capacity levels and superoxide dismutase, catalase, glutathione peroxidase activities in operative patients with gastrointestinal cancer before and after surgery and compare with inoperative patients.

Methods

Oxidative stress parameters were measured in 59 gastrointestinal cancer patients and 20 controls. 8-hydroxy-deoxyguanosine was quantitated by Elisa method. Superoxide dismutase, catalase, glutathione peroxidase were assayed with colorimetric methods; Nitrite + nitrate, total glutathione and total antioxidant capacity were assayed with spectrophotometric methods.

Results

8-hydroxy-deoxyguanosine levels in cancer patients were higher than those of control group (p < 0.01). Similarly, glutathione levels were increased compared with controls (p < 0.01). However, nitrite + nitrate, total antioxidant capacity levels and superoxide dismutase and catalase activities were decreased in cancer patients compared with controls (p < 0.01, p < 0.01, p < 0.05, p < 0.01, respectively). The patients were divided into two groups; operative (n = 30) and inoperative (n = 29). A significant difference was found in inoperative group compared with postoperative group according to glutathione peroxidase activity (p < 0.05).

Discussion

Our results demonstrate that the oxidant/antioxidant balance was altered in favor of free radicals and DNA damage in gastrointestinal cancer patients. Significant increases in 8-hydroxy-deoxyguanosine, glutathione and decreases in nitrite + nitrate, SOD, CAT activities and antioxidant molecules suggest the possible involvement of oxidative stress in gastrointestinal cancer. Glutathione peroxidase activities in postoperative patients were higher compared to inoperative patients.

Introduction

Reactive oxygen species have highly harmful effects on cellular macromolecules such as DNA, lipid and proteins of living organisms [1]. Free radical mediated oxidative damage in cancer has been shown in various studies [2], [3], [4]. The harmful effects and biological damage caused by these species is termed oxidative stress [5], [6]. Unfavorable side effects occur when there is an imbalance between overproduction of reactive oxygen species and decrease of antioxidant molecules in body. DNA is highly susceptible to free radical attacks. Modification of DNA is considered to be the most important consequence of oxidative stress, and it can become permanent via the formation of mutations and other types of genomic instability. Most interest has been on measuring 8-hydroxy-deoxyguanosine as a sensitive biomarker for oxidative DNA damage [7]. Numerous papers in recent years have analyzed levels of 8-hydroxy-deoxyguanosine in tissue, leukocyte and urine of cancer patients in relation to oxidative stress. 8-hydroxy-deoxyguanosine levels in patients with various cancers were also significantly higher than those in control subjects [8], [9], [10], [11].

Plasma contains a large number of antioxidants, some of which prevent the initiation of the process of oxidation while others inhibit the further progression of the cascade of reactions in carcinogenesis [12]. While antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase are responsible for intracellular protection, nonenzymatic molecules are involved in extracellular defense [13]. Superoxide dismutase catalyzes the dismutation reaction of the toxic superoxide radical to molecular oxygen and hydrogen peroxide. Glutathione peroxidase catalyzes the peroxidation of hydrogen peroxide in the presence of reduced glutathione to form water and oxidized glutathione. Catalase protects from oxidative stress by catalyzing the rapid decomposition of hydrogen peroxide to oxygen and water. The role of antioxidant enzymes in cancer has been the subject of much controversy. The activities of these enzymes were reported to be increased, decreased or unchanged in various cancers [14], [15], [16]. Glutathione is the major endogenous soluble antioxidant molecule in mammalian cells. It provides protection against oxidative stress through serving as a substrate for the antioxidant enzymes glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase that convert peroxides into less harmful fatty acids, water and glutathione disulfide. It is also able to protect cells against oxidative stress by non-enzymic scavenging of free radicals [17]. A decrease of blood glutathione in circulation has been reported in liver cancer [18], but there is publication where the increase in its concentration has been shown in patients with some malignancies [19].

The aim of this study was to investigate changes in 8-hydroxy-deoxyguanosine, nitrite + nitrate, total glutathione, total antioxidant capacity levels and superoxide dismutase, catalase, glutathione peroxidase activities in operative patients before and after operation and compare with inoperative patients with gastrointestinal cancer and healthy individuals.

Section snippets

Patients

We studied 59 patients with newly diagnosed gastrointestinal cancer (mean age, 53.10 ± 1.83 years; 38 men and 21 women) and 20 age-matched control subjects (mean age, 46.85 ± 3.02 years; 8 men and 12 women) at Ankara Oncology Educational and Research Hospital, Ankara, Turkey. Of the 23 patients with gastric cancer, 18 had rectum cancer, 11 had colon cancer, 4 had pancreas cancer, 2 had liver cancer and 1 had esophageal cancer. The study was approved by Ankara Oncology Educational and Research

Results

Distribution of gastrointestinal cancer diagnoses in patients is summarized in Table 1. The clinical characteristics and laboratory data from patients with gastrointestinal cancer and healthy subjects are given in Table 2. The levels of HDL-cholesterol in cancer group were statistically lower than those of control group (p < 0.01). No significant differences were determined in the comparison of total cholesterol, LDL-cholesterol and triglycerides levels between cancer group and controls (p > 0.05).

Discussion

Reactive oxygen species are indispensable as mediators in many normal cellular processes, but when produced excessively and/or during inadequate antioxidant protection, can cause oxidative damage to DNA, proteins and lipids. Formation of 8-hydroxy-deoxyguanosine is regarded as a useful indicator of oxygen radical-induced DNA damage [7]. This study showed a significantly higher level of 8-hydroxy-deoxyguanosine, and thus oxidative DNA damage, in gastrointestinal cancer patients compared to

Learning points

•
We found that there were severe oxidative stress in the gastrointestinal cancer.
•
These findings suggested the possibility that increased oxidative stress may be associated with gastrointestinal cancer.
•
Glutathione peroxidase activities in postoperative patients were higher compared to inoperative patients.

Conflict of interest

The authors had no conflicts of interest to declare in relation to this article.

Acknowledgments

This study was supported by Gazi University Research Foundation (02/2006-5, 02/2006-6).

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Original articleIncreased oxidative DNA damage and impaired antioxidant defense system in patients with gastrointestinal cancer

Abstract

Background

Methods

Results

Discussion

Introduction

Section snippets

Patients

Results

Discussion

Learning points

Conflict of interest

Acknowledgments

Urology

Cancer Detect Prev

Biochim Biophys Acta

Toxicology

Clin Biochem

J Chromatogr B

Nutr Res

Biomed Environ Sci

Clin Biochem

Free Radic Biol Med

Clin Biochem

Clin Biochem

J Psychosom Res

Cell

Biochim Biophys Acta

J Urol

Free Radic Biol Med

Biomed Environ Sci

Eur J Intern Med

Biomed Environ Sci

Clin Biochem

Cancer Lett

Original article
Increased oxidative DNA damage and impaired antioxidant defense system in patients with gastrointestinal cancer