The yields of DNA single (ssb)- and double-strand breaks (dsb) as well as base lesions, which are converted into detectable ssb by base excision repair enzymes, induced at 278 K by densely ionizing alpha-radiation have been determined as a function of the level of hydration (Gamma, number of water molecules per nucleoticle) of films of supercoiled plasmid DNA (pUC 18). The yields of prompt ssb induced by alpha-radiation are independent of Gamma, from vacuum-dried up to 35 water molecules per nucleotide, indicating that diffusible hydroxyl radicals or H2O.+, if induced in the hydrated layer by alpha-radiation, do not significantly contribute to the induction of ssb. In contrast, the yield of prompt dsb does increase with increasing hydration level. At a Gamma of 35, the yield of dsb is about twice that for gamma-irradiation. Treatment of alpha-particle-irradiated DNA with the enzymatic probes, endonuclease III (Nth), and formamidopyrimicline-DNA glycosylase (Fpg), does not lead to significant levels of additional ssb and dsb. It is proposed that (i) base lesions induced by direct energy deposition in the DNA-water complex by high LET radiation, such as cc-particles, are generally present in clustered DNA damage, e.g., two or more lesions produced within a few tens of base pairs, and (ii) the complexity of the clustered damage, lesion density, is greater for densely (compared with sparsely) ionizing radiation. As a consequence, the majority of DNA base lesions induced by high LET radiation, in contrast to those by low LET radiation, and which are substrates for Fpg and Nth become refractory to excision repair due to their formation within more complex, clustered DNA damage.