Cytotoxicity of [125I]iodoHoechst 33342: contribution of scavengeable effects.
OBJECTIVE
The incubation of the DNA minor-groove binder [125I]iodoHoechst 33342 (125IH) with plasmid DNA leads to the production of one double-strand break (dsb) per decay, both in the presence and absence of dimethylsulfoxide (DMSO). In contrast, when 125I is incorporated into mammalian cell DNA as an iodinated pyrimidine base, DMSO decreases the dsb yield and enhances survival. Because these variations in radioprotective effects may be due either to the location of 125I vis-à-vis the DNA helix or to differences in DNA architecture, the toxicity of 125IH and its modification by DMSO were examined in mammalian cells.


METHODS
Uptake and retention of 125IH in V79 cells were measured, and survival was determined after accumulation of 125I decays at 0.3 degrees C +/-10% DMSO.


RESULTS
A linear-quadratic survival curve was obtained both in the absence [D37 = 114+/-36 decays/cell, alpha = (5.39 1.17) x10(-3) cell/decay] and presence [D37 = 211+/-65 decays/cell, alpha = (1.27+/-0.52) x10(-3) cell/decay] of DMSO. The dose modification factor for the linear component of the survival curve was 4.25+/-1.97, indicating the predominance of indirect mechanisms. This value is similar to that obtained with DNA-incorporated 125I (4.05+/-1.72) and for the initial slope (alpha) of 137Cs gamma-rays (4.43+/- 1.41).


CONCLUSIONS
Cytotoxicity resulting from the decay of the Auger electron emitter 125I in the mammalian cell nucleus is caused mainly by indirect mechanisms.
Walicka
M A
MA
Department of Radiology, Harvard Medical School, Boston, MA 02115, USA.
Ding
Y
Y
Roy
A M
AM
Harapanhalli
R S
RS
Adelstein
S J
SJ
Kassis
A I
AI
D000818:Animals; D001562:Benzimidazoles / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007457:Iodine Radioisotopes / Q000378:metabolism / Q000633:toxicity; D008168:Lung / Q000166:cytology; D009690:Nucleic Acid Conformation; D019275:Radiopharmaceuticals / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*
D001562:Benzimidazoles; D016166:Free Radical Scavengers; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D004247:DNA; C017807:bisbenzimide ethoxide trihydrochloride; D004121:Dimethyl Sulfoxide