DNA strand breaks and repair in lymphocytes after chronic low dose oxidant stress in vivo

In contrast to the well-documented negative effects of high dose oxidant exposure, accumulating evidence supports a positive, perhaps essential physiologic role for very low level oxidant stress. For example, low level oxidant exposure, within or below the physiologic range, has been reported to stimulate membrane signal transduction, proliferation, antioxidant defense, and DNA repair. In the present study, the authors pursue the possibility that whole body exposure to low dose radiation (LDR) induces an up-regulation in the accumulation and repair of DNA strand breaks in lymphocytes. C57BI/6 mice were exposed for 4 weeks to 0.04 Gy/day of {gamma} radiation as a model of low level oxidant stress. End points measured in spleen cells after chronic in vivo LDR included; (1) constitutive expression of DNA strand breaks; (2) sensitivity to oxidant-induced DNA damage; (3) repair of DNA strand breaks after mitogen stimulation; (4) ADP-ribosyl transferase (ADPRT) activity. The results indicated that the constitutive level of DNA strand breaks was significantly decreased after chronic LDR, and associated with a decrease in ADPRT activity. However, DNA repair capacity was not enhanced relative to sham-irradiated mice. These results suggest that cumulative DNA damage and associated repair activity are both adaptively reduced after chronic LDR andmore » may reflect an up-regulation in mechanisms of antioxidant defense.« less