Increase in DNA single-strand break rejoining by continuous exposure of human mononuclear blood cells to radioiodine ((131)I) in vitro.
Radioiodine ((131)I) induced a dose- and time-dependent increase in DNA single-strand breaks (DNA-ssb) in human (G0) mononuclear blood cells (MNC) in vitro. Incubation of MNC with 22MBq (131)I/ml at 4 degrees C caused a linear, time-dependent induction of DNA-ssb (increase in elution rate: 24.7 x 10(-3) h(-1) per 100 min incubation with (131)I). However, 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 with 22 or 30 MBq (131)I/ml. The goodness of fit of different regression models was assessed by Akaike's Information Criterion (AIC). The best fit was obtained for a non-linear model (y=a+bx+cx(0.5); AIC=53.5; where x is incubation time and y is elution rate), whereas other models including the linear regression model y=a+bx; AIC=38.6) were worse. As the total induction of DNA-ssb at 4 degrees C was constant with time, the 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 DNA-ssb. Inhibition of both RNA and protein synthesis clearly increased the extent of DNA-ssb observable after incubation with (131)I. Thus, during continuous exposure of MNC to (131)I, proteins were synthesized which rejoined DNA-ssb. However, incubation of MNC with (131)I (44 MBq/ml) at 37 degrees C under conditions expected to lead to inhibition of RNA and/or protein synthesis still resulted in a decrease of the slope of the time effect curve, indicating a stimulation of DNA-ssb rejoining. Thus, we favour the hypothesis that the increase in the activity of DNA-ssb rejoining, besides de novo synthesis of repair enzymes, is also caused by a post-translational stimulation of DNA-repair enzymes and that this stimulation possibly is mediated by DNA-fragments.
Hengstler
J G
JG
Institute of Toxicology, University of Mainz, Germany.
Bockisch
A
A
Fuchs
J
J
Grimm
W
W
Zapf
A O
AO
Lade
K
K
Meinert
R
R
Oesch-Bartlomowicz
B
B
Tanner
B
B
Oesch
F
F
D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007457:Iodine Radioisotopes / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000528:radiation effects; D014176:Protein Biosynthesis
D004277:DNA, Single-Stranded; D007457:Iodine Radioisotopes