Daily variations of plasma malondialdehyde levels in patients with early breast cancer

doi:10.1016/S0361-090X(03)00029-1

Cancer Detection and Prevention

Volume 27, Issue 2, 2003, Pages 122-126

https://doi.org/10.1016/S0361-090X(03)00029-1 Get rights and content

Abstract

In this study, we aimed to investigate the diurnal variations of malondialdehyde (MDA), in patients with early breast cancer. Ten consecutive premenopausal patients with early stage breast cancer and 10 healthy volunteers were included. Blood samples were taken every 4 h for a period of 24 h. The peripheral blood cells were counted and the plasma MDA levels measured as an indicator of lipid peroxidation. The daily average MDA levels of the patients were significantly higher than that of the controls (2.7±0.2 μmol/ml versus 2.2±0.2 μmol/ml, P=0.044, respectively). The plasma MDA levels of the patients showed significant diurnal variations with the highest levels at 20:00 h and the lowest levels at 04:00 h. In the control group, the plasma MDA levels had no statistically significant diurnal variations. However, the MDA levels at 12:00 and 16:00 h were significantly higher than the levels at 04:00 h. The MDA levels of the patients group were significantly correlated with WBC and neutrophils with a phase difference of 12 h (ρ=0.341, P=0.012 and ρ=0.288, P=0.035, respectively). Though there were weak correlations between the MDA levels and WBC and neutrophils in the control group (ρ=0.215, P=0.127 and ρ=0.249, P=0.076, respectively), the phase difference was 8 h. In conclusion, the current cross-sectional study suggests that the phase differences in daily variations of lipid peroxidation may play a role in carcinogenesis.

Introduction

Oxidative stress, especially lipid peroxidation, is known to be involved in carcinogenesis [1]. Increased levels of lipid peroxidation products play a role in the early phases of tumor growth [2], [3]. Malondialdehyde (MDA), a natural product of lipid peroxidation and prostaglandin biosynthesis, is known to induce carcinogenesis [1]. Furthermore, the endogenous MDA has also been reported to cause mutagenesis in various tissues by forming DNA adducts [4].

Plasma MDA levels have been studied as an indicator of lipid peroxidation in humans. Different results with regard to the levels of lipid peroxidation products, especially MDA, in various tumors including breast cancer have been reported. Gerber et al. [5] have reported that patients with breast cancer have significantly lower plasma MDA levels when compared to healthy controls. Therefore, they hypothesized that the patients with cancer have a picture of lower lipid peroxidation. Conversely, Faber et al. [6] and Huang et al. [7], have shown that the patients with breast cancer have higher MDA levels when compared to controls. Therefore, the previous studies reporting conflicting results with regard to the levels of oxidants in cancer patients do not give any support for the in vivo carcinogenic potential of the increased levels of lipid peroxidation products.

The daily changes of plasma MDA levels may explain the differences of various conflicting reports on the relations of plasma MDA levels and tumors. However, there is little knowledge about the daily variations of plasma MDA levels. In some previous reports, plasma MDA and urinary MDA levels in healthy subjects have been reported to show significant diurnal variations [8], [9], [10]. One of the potential sources for plasma MDA is peripheral blood cells. The circadian changes of white blood cells (WBC) and neutrophils could explain the diurnal variations of plasma MDA levels seen in both healthy subjects and in cancer patients with early stages [11], [12], [13].

In this cross-sectional study, we aimed to study the daily variations of plasma MDA levels and its correlation with WBCs in patients with early breast cancer.

Section snippets

Patients and methods

Ten consecutive premenapousal patients with stages I–II breast cancer were included in the study. The median age of the patients was 37 years (range: 30–45 years). Also, 10 healthy women with a median age of 34 yeras (range 20–48 years) were included in the control group. None of the controls and patients had any hematological, endocrine and metabolic abnormalities and none were taking any medication that may affect the levels of measured parameters.

Peripheral blood samples were taken six times

Results

The measured levels of plasma MDA, WBC and neutrophil counts, for both groups are shown in Table 1.

The daily average MDA levels of the patient group were found to be significantly higher in the patient group when compared to controls (2.7±0.2 versus 2.2±0.2 μmol/ml, P=0.044, respectively) at the 24 h basis. However, when the results were analyzed according to the measurement time periods in a day, only the MDA levels at 20:00 h were significantly higher in the patients group than those of the

Discussion

Endogenous MDA formation and the data on its mutagenicity suggest the possible role of this molecule in carcinogenesis [2]. The potential of MDA in formation of DNA adducts and as a cofactor in formation of cathecolestrogen metabolites have been proposed for its role in estrogen-induced carcinogenesis [15]. In experimental rodent models of carcinogenesis, MDA have been reported as an important biomarker for chemoprevention [16], [17].

There have been conflicting reports with regard to the levels

References (22)

M.A. Trush et al.
An overview of the relationship between oxidative stress and chemical carcinogenesis
Free Radic. Biol. Med.
(1991)
C. Rice-Evans et al.
Free radical-lipid interactions and their pathological consequences
Prog. Lipid Res.
(1993)
L.J. Marnett
Lipid peroxidation-DNA damage by malondialdehyde
Mutat. Res.
(1999)
Y.L. Huang et al.
Association between oxidative stress and changes of trace elements in patients with breast cancer
Clin. Biochem.
(1999)
M. Gerber et al.
Tumor progression and oxidant–antioxidant status
Cancer Lett.
(1997)
B.J. Rodgers et al.
Fluctuations in DNA synthesis by mammary tissue from the pregnant hamster
Comp. Biochem. Physiol. B
(1983)
B.N. Ames
Dietary carcinogens: oxygen radicals and degenerative diseases
Science
(1983)
M. Gerber et al.
Relationship between vitamin E and poly-unsaturated fatty acids in breast cancer. Nutritional and metabolic aspects
Cancer
(1989)
M. Faber et al.
Lipid peroxidation products, and vitamin and trace element status in patients with cancer before and after chemotherapy including adriamycin. A preliminary study
Biol. Trace Elem. Res.
(1995)
A.B. Bridges et al.
Circadian variation of white blood cell aggregation and free radical indices in men with ischaemic heart disease
Eur. Heart J.
(1992)

H. Kosugi et al.

Characteristics of the thiobarbituric acid reactivity of human urine as a possible consequence of lipid peroxidation

Lipids

(1993)

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Daily variations of plasma malondialdehyde levels in patients with early breast cancer

Abstract

Introduction

Section snippets

Patients and methods

Results

Discussion

Free Radic. Biol. Med.

Prog. Lipid Res.

Mutat. Res.

Clin. Biochem.

Cancer Lett.

Comp. Biochem. Physiol. B

Dietary carcinogens: oxygen radicals and degenerative diseases

Science

Relationship between vitamin E and poly-unsaturated fatty acids in breast cancer. Nutritional and metabolic aspects

Cancer

Lipid peroxidation products, and vitamin and trace element status in patients with cancer before and after chemotherapy including adriamycin. A preliminary study

Biol. Trace Elem. Res.

Circadian variation of white blood cell aggregation and free radical indices in men with ischaemic heart disease

Eur. Heart J.

Characteristics of the thiobarbituric acid reactivity of human urine as a possible consequence of lipid peroxidation

Lipids