DNA strand breaks and DNA repair response in lymphocytes after chronic in vivo exposure to very low doses of ionizing radiation in mice.
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, we have examined whether whole-body exposure to low-dose radiation (LDR) results in an alteration in constitutive (steady state) levels of DNA-strand breaks and whether an adaptive increase in DNA-repair response is induced. C57B1/6J mice were exposed to 0.04 Gy (4 cGy) of gamma-radiation as a model of low level oxidant stress. End points measured after chronic in vivo LDR included: (1) constitutive expression of DNA-strand breaks in quiescent spleen cells; (2) sensitivity to DNA damage after high-dose radiation exposure in vitro; (3) repair of constitutive and radiation-induced DNA strand breaks after mitogen stimulation: (4) activity of the DNA-repair associated enzyme, poly(ADP-ribose)transferase (ADPRT) and its substrate, NAD. The results indicated that the constitutive expression of DNA-strand breaks is significantly decreased after chronic LDR; however, DNA-repair capacity after high-dose radiation exposure is not increased above that observed in sham-irradiated mice. Associated with the reduction in constitutive DNA-strand break accumulation was a decrease in resting levels of the DNA-repair-associated enzyme poly(ADP-ribose) transferase (ADPRT). These results are consistent with the interpretation that cumulative DNA damage and associated DNA-repair activity in unstimulated cells are both reduced after chronic LDR exposure.
James
S J
SJ
Geriatric Research, Education and Clinical Center, VA Medical Center West Los Angeles, CA 90077.
Enger
S M
SM
Makinodan
T
T
D000228:Adenine Phosphoribosyltransferase / Q000235:genetics; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D051379:Mice; D008810:Mice, Inbred C57BL; D009243:NAD / Q000032:analysis; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000528:radiation effects*; D014916:Whole-Body Irradiation
D009243:NAD; D000246:Adenosine Diphosphate Ribose; D000228:Adenine Phosphoribosyltransferase