Effects of physical activity on systemic oxidative/DNA status in breast cancer survivors

Abstract

Physical activity offers a paradoxical hormetic effect and a health benefit to cancer survivors; however, the biochemical mechanisms have not been entirely elucidated. Despite the well-documented evidence implicating oxidative stress in breast cancer, the association between health benefits and redox status has not been investigated in survivors who participate in dragon boating. The present study investigated the plasmatic systemic oxidative status (SOS) in breast cancer survivors involved in two distinct physical training exercises. A total of 75 breast cancer survivors were allocated to one of three groups: Control (resting), dragon boat racing and walking group; the latter is a type of aerobic conditioning exercise often advised to cancer patients. Various biochemical oxidative stress markers were examined, including oxidant status (hydroperoxide levels, lipid oxidation) and antioxidant status (enzymatic activities of superoxide dismutase and glutathione peroxidase, reduced glutathione levels and antioxidant capability). In addition, the individual DNA fragmentation and DNA repair capability of nucleotide excision repair (NER) systems were examined by comet assays. According to the results, all patients exhibited high levels of oxidative stress. Physical activity maintained this oxidative stress condition but simultaneously had a positive influence on the antioxidant component of the SOS, particularly in the dragon boat racing group. DNA fragmentation, according to the levels of single- and double-strand breaks, were within the normal range in the two survivor groups that were involved in training activities. Radiation-induced damage was not completely recognised or repaired by NER systems in any of the patients, probably leading to radiosensitivity and/or susceptibility of patients to cancer. These findings suggest that physical activity, particularly dragon boat racing, that modulates SOS and DNA repair capability could represent a strategy for enhancing the quality of life and improving the long-term health benefits for breast cancer survivors.

Keywords: breast cancer; comet assay; dragon boating; glutathione; nucleotide excision repair; superoxide dismutase activity; systemic oxidative status.

Figure 1.

Determination of systemic oxidative status in breast cancer survivors. (A) d-ROMs test results; the levels of oxidative stress are expressed in CARR U (1 CARR U=H₂O₂ 0.08 mg/dl; control range, 250–300 CARR U). (B) Plasmatic LPO levels are expressed as nmol/ml (control range 8–10 nmol/ml). (C) BAP test represents the power of antioxidant capability and is expressed as µmol/l (control range, >2200 µmol/l). (D) Total plasmatic thiol groups are expressed as µmol/ml (control range, 0.4–0.6 µmol/ml). (E) SOD activity is expressed as U/ml (control values, 1.82±0.039 U/ml). (F) GPx activity values are expressed in nmol/min/ml (control values, 113.41±20.77 nmol/min/ml). For each group, the line in the middle of the box represents the median, the black dash represents the mean value, and the lower and the upper edges of the box represent the 1st and 3rd quartiles, respectively. Whiskers represent the minimum and maximum values; observations denoted as black circles are considered outliers. The thick black line on the y-axis of the graph indicates the range of the healthy control group at rest (n=30). ***P<0.001; **P<0.01; *P<0.05. Group A, dragon boat racing group; Group B, walking group; Control BrC, breast cancer survivors at rest; d-ROMs, derivatives of reactive oxygen metabolites; LPO, lipid hydroperoxides; BAP, biological plasmatic antioxidant potential; SOD, superoxide dismutase; GPx, glutathione peroxidase.

Figure 2.

DNA damage in breast cancer survivors. (A) Total DNA damage measured by alkaline and (B) double-strand breaks measured by neutral comet assays following physical training (Groups A and B) or rest (Control BrC). The results are expressed as % TDNA, i.e. the percentage of DNA in the comet tail. For each group, the line in the middle of the box represents the median, the black dash represents the mean value, and the lower and the upper edges of the box represent the 1st and 3rd quartiles, respectively. Whiskers represent the minimum and maximum values; observations denoted as black circles are considered outliers. The thick black line on y-axis of the graph indicates the range of control values. Group A, dragon boat racing group; Group B, free walking group; Control BrC, breast cancer survivors at rest.

Figure 3.

Nucleotide excision repair capability in breast cancer survivors. Naked DNA from ultraviolet C-irradiated human umbilical vein endothelial cells were incubated in gel with buffer, or T4 endonuclease V, or lymphocyte extracts from each subject. Following 45 min of incubation, DNA breaks introduced by repair endonuclease activity in the lymphocyte extracts were measured by comet assay and expressed as % TDNA, i.e. the percentage of DNA in the comet Tail. For each group, the line in the middle of the box represents the median, the black dash represents the mean value, and the lower and the upper edges of the box represent the 1st and 3rd quartiles, respectively. Whiskers represent the minimum and maximum values; observations denoted as black circles are considered outliers. The dotted line represents the calculated % TDNA (percentage of DNA in the comet tail) from T4 endonuclease V, which was considered as reference value for evaluating patients repair capability. **P<0.01; *P<0.05. Group A, dragon boat racing group; Group B, walking group; Control BrC, breast cancer survivors at rest.