Retinoblastoma: Magnetic Isotope Effects Might Make a Difference in the Current Anti-Cancer Research Strategy

Abstract

A B ST R AC T Human retinoblastoma cells were proven to possess some very unusual DNApolβ species. Being 23.5 kDa monomers, which itself is not common for the DNApolβ superfamily members, these chromatin associated proteins manifests most of the DNApolβ-specifc functional peculiarities making them legitimate targets for DNA repair cytostatic inhibitors. Particularly, these tumor specific enzymes were found to be very sensitive to -promoted magnetic isotope effects (MIE) caused a marked DNA sequence growth limitation as well as a formation of the size-invalid, i.e. too short in length, DNA fragments, totally inappropriate for the DNA repair purpose. This MIE-DNApolβ match may serve a starting point for further move towards the paramagnetic path in current developments of anti-cancer strategies.K E Y WO R D S retinoblastoma; magnetic isotope effects (MIE); DNA repair

Ultrashort ssDNA in Retinoblastoma Patients Blood Plasma Detected by a Novel High Resolution HPLC Technique: a Preliminary Report

“…A remarkably high detection sensitivity of our SE-AE-HPLC technique is no doubt helpful for further studies aiming to find out a link between the DNA repair damages in carcinogenesis and the appearance of the broken DNA repair products, short ssDNA (1,2), in the patients blood plasma. So our method is to be treated as a reliable tool for both oncogenesis research and laboratory diagnostics purposes.…”

“…Moreover, the PCR engaging DNA size measurement might be an inadequate choice once these DNA fragments have the DNA repair related origin. In this case, the release of ssD-NA species would occur in the DNA repair process usually accelerated in malignancies (1)(2)(3)(4).…”

“…The DNA repair machinery damage involves a marked DNA polymerase β hyperexpression and its processivity limitations in retinoblastoma cells (1,2). This may promote some tumor DNA release as long as the DNA repair related short polydeoxyribonucleotides are going to get lost in a chaotic modulation of chromatin structure (3)(4)(5).…”

“…To reveal such a contribution, the extra-high resolution ssDNA-detecting tool is needed. It is hardly possible to overestimate this requirement since the conventional agarose gel electrophoresis and PCR procedures are not selective and sensitive enough as long as the pg-ng concentration range for short (smaller than 100n) ssDNA detection in clinical samples is the case (1)(2)(3)(4)(5).…”

Magnetic Control of the DNA Synthesis by Nuclear Magnetic Ions of Mg, Ca and Zn as a Powerful and Universal Means to Kill Cancer Cells

“…At the identical conditions the polβ loaded with 25 Mg 2+ , 43 Ca 2+ , 67 Zn 2+ ions exhibited strong inhibitory effect for both sorts of cells decreasing the yield of DNA by 2-3 times with respect to ions 24 Mg 2+ , 40 Ca 2+ , 64 Zn 2+ . The other benefit of nuclear magnetic ions is that they produce, like in the case of HL-60 cells, the short, "invalid" DNA segments inefficient for the DNA repair [35]. Nuclear spin-carrying isotopic ions 25 Mg 2+ , 43 Ca 2+ , 67 Zn 2+ were shown to promote the marked magnetic isotope effects on polymerase β in ex vivo survived human retinoblastoma cells; they promote the essential, by 2−3 times, inhibitory effect on the DNA synthesis in these cells (Figures 11 and 12) and lead to the sharp increase of cancer cell mortality [35,36].…”