Effect of nitric oxide and malondialdehyde on sister-chromatid exchanges in breast cancer

Nitric oxide (NO) and malondialdehyde (MDA) play a significant role in DNA damage, sister-chromatid exchanges (SCEs) and carcinogenesis. Here, we determine plasma NO and MDA to evaluate their role in carcinogenesis and their effect on the frequency of SCEs in 45 female breast cancer patients and in 35 age- and sex-matched controls. Plasma NO (P<0.01) and MDA (P<0.001) was significantly higher in the breast cancer group, and a direct correlation were found between plasma NO and MDA concentration and tumour grade. Patients with stage II disease showed the highest levels of both NO and MDA, compared with controls. Simultaneously, SCE frequency per lymphocyte in the breast cancer group was found to be significantly (P<0.001) higher; the greatest increase being found in patients with stage IV disease. Positive correlation was found between SCEs and both NO and MDA in the breast cancer group; however, both NO and MDA production decreased with increasing severity of the disease. Lower NO production in stage IV disease may be due to lower expression of nitric oxide synthase (NOS), further facilitating the production of superoxide anions (O2*-). The reaction between NO and O2*- results in peroxynitrite (OONO-) formation, which works efficiently at the molecular level and may induce higher SCE frequency. This work suggests that further cytogenetic and molecular study is required to provide definite answers for the therapeutic use of NO in breast cancer.