INCREASE IN DNA SINGLE-STRAND BREAK REJOINING BY CONTINUOUS EXPOSURE OF HUMAN MONONUCLEAR BLOOD-CELLS TO RADIOIODINE (I-131) IN-VITRO

Radioiodine (I-131) induced a dose-and time-dependent increase in DNA single-strand breaks (DNA-ssb) in human (G(0)) mononuclear blood cells (MNC) in vitro. Incubation of MNC with 22 MBq I-131/ml at 4 degrees C caused a linear, time-dependent induction of DNA-ssb (increase in elu tion rate: 24.7 x 10(-3) h(-1) per 100 min incubation with I-131). How ever, if MNC were incubated at 37 degrees C a decrease in the slope of the time-effect curve was observed after about 300 min incubation wit h 22 or 30 MBq I-131/ml. The goodness of fit of different regression m odels was assessed by Akaike's Information Criterion (AIC). The best f it was obtained for a non-linear model (y=a+bx+cx(0.5); AIC=535; where x is incubation time and y is elution rate), whereas other models inc luding the linear regression model (y=a+bx; AIC=38.6) were worse. As t he total induction of DNA-ssb at 4 degrees C was constant with time, t he decrease in the slope of the time-effect curve (DNA-ssb versus time ) at 37 degrees C can be interpreted as an increase in rejoining of DN A-ssb. Inhibition of both RNA and protein synthesis clearly increased the extent of DNA-ssb observable after incubation with I-131. Thus, du ring continuous exposure of MNC to I-131, proteins were synthesized wh ich rejoined DNA-ssb. However, incubation of MNC with I-131 (44 MBq/ml ) at 37 degrees C under conditions expected to lead to inhibition of R NA and/or protein synthesis still resulted in a decrease of the slope of the time-effect curve, indicating a stimulation of DNA-ssb rejoinin g. Thus, we favour the hypothesis that the increase in the activity of DNA-ssb rejoining, besides de novo synthesis of repair enzymes, is al so caused by a post-translational stimulation of DNA-repair enzymes an d that this stimulation possibly is mediated by DNA-fragments.