Reexamining the Mössbauer effect as a means to cleave DNA

The ability of a DNA-bound Mössbauer isotope to absorb resonant gamma-radiation and subsequently, upon decay, induce DNA double-strand breaks by emission of low-energy Auger electrons was examined with a simple plasmid DNA cleavage assay. This mechanism was postulated by Mills et al. [Mills et al. (1988) Nature 336, 787] in the observed ablation of tumor cell growth with 57Fe(III)-bleomycin and Mössbauer radiation. The observed linearization of supercoiled pAA15 plasmid DNA upon treatment with five or more 57Fe(III)-bleomycin per plasmid precluded its use for testing Mössbauer effect induced cleavage. An alternative 57Fe-DNA-binding complex, [57Fe(phen)2(DPPZ)](PF6)2.H2O (57(1)), was synthesized and found to tightly bind DNA (K = 9.8 x 10(5) M-1) yet not induce DNA nicks or cuts at loadings of less than 500/pAA15 plasmid. Mössbauer irradiation of 57(1)/pAA15 samples under frozen and solution conditions does not result in observable linearization of the plasmid DNA over control samples. Some linearization is observed in all irradiated samples but is attributed only to the photoelectric effect.