Cytotoxicity of [ 125 I]iodoHoechst 33342: contribution of scavengeable effects

Abstract

Purpose: The incubation of the DNA minor-groove binder [ 125 I]iodoHoechst 33342 (125 IH) 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 125 I 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 125 I vis-a-vis the DNA helix or to differences in DNA architecture, the toxicity of 125 IH and its modification by DMSO were examined in mammalian cells. Methods: Uptake and retention of 125 IH in V79 cells were measured, and survival was determined after accumulation of 125 I decays at 0.3 ° C +/- 10% DMSO. Results: A linear-quadratic survival curve was obtained both in the absence [D 37 = 114 + 36 decays/cell, alpha = (5.39 +/- 1.17)x 10 -3 cell/decay] and presence [ D 37 = 211 +/- 65 decays/cell, alpha = (1.27 +/- 0.52)x 10 -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 125 I (4.05 +/- 1.72) and for the initial slope (alpha) of 137 Cs gamma-rays (4.43 +/- 1.41). Conclusions: Cytotoxicity resulting from the decay of the Auger electron emitter 125 I in the mammalian cell nucleus is caused mainly by indirect mechanisms.