Effects of low dose pre-irradiation on hepatic damage and genetic material damage caused by cyclophosphamide

Cyclophosphamide (CTX) can attack tumour cells, but can also damage the other cells and microstructures of an organism at different levels, such as haematopoietic cells, liver cells, peripheral lymphocyte DNA, and genetic materials. Low dose radiation (LDR) can induce general adaptation reaction. In this study, we explore the effects of low dose radiation on hepatic damage and genetic material damage caused by CTX.

Mice were implanted subcutaneously with S180 cells in the left groin (control group excluded). On days 8 and 11, mice of the LDR and LDR+CTX groups were given 75 mGy of whole-body γ-irradiation; whereas mice of the CTX and LDR+CTX groups were injected intraperitoneally with 3.0 mg of CTX. All mice were sacrificed on day 13. DNA damage of the peripheral lymphocytes, alanine aminotransferase (ALT) activity, total protein (TP), albumin (ALB) of the plasma, malonyl-dialdheyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity of the hepatic homogenate, and micronucleus frequency (MNF) of polychromatoerythrocytes in the bone marrow were analysed.

The control group had the lowest MDA content and the highest SOD and GSH-PX activity, whereas the CTX group had the highest MDA content and the lowest SOD and GSH-PX activity. Compared with the CTX group, the MDA content decreased significantly (p < 0.01) and the SOD and GSH-PX activity increased significantly (p < 0.05) in the LDR+CTX group. TP and ALB in control group were higher than that of the other groups. Compared with the sham-irradiated group, TP and ALB in the LDR group elevated significantly (p < 0.05). The control group had the lightest DNA damage, whereas the CTX group had the severest. DNA damage in LDR+CTX group was much lighter compared with that of the CTX group (p < 0.05). MNF in the CTX group increased significantly compared with the control and the sham-irradiated groups (p < 0.01). Compared with the CTX group, MNF in LDR+CTX group had a tendency of decline, but without statistical significance (p > 0.05).

Pre-chemotherapeutic LDR can induce the activities of anti-oxidative enzymes and promote the elimination of free radicles to alleviate the damaging effects of oxidative stress to hepatic tissue caused by high-dose CTX. At the same time, LDR has no obvious effect on the ALT activity of plasma, but may have protective effect on the protein synthesis function of the liver. High-dose CTX chemotherapy can cause DNA damage of peripheral lymphocytes; however, LDR before chemotherapy may have certain protective effect on DNA damage. Moreover, CTX has potent mutagenic effect; however, LDR may have no protective effect against the genetic toxicity of CTX chemotherapy.