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
Background: Macrophages (ML) can be M1/M2 polarized by Th1/2 signals, respectively. M2-like ML are thought to be important in asthma pathogenesis, and M1-like in anti-infective immunity, however their roles in virus-induced asthma exacerbations are unknown. Our objectives were (i) to assess polarised ML phenotype responses to rhinovirus (RV) infection in vitro and (ii) to assess ML phenotypes in healthy subjects and people with asthma before and during experimental RV infection in vivo. Methods: We investigated characteristics of polarized/unpolarized human monocyte-derived ML (MDM, from 3À6 independent donors) in vitro and evaluated frequencies of M1/M2-like bronchoalveolar lavage (BAL) ML in experimental RV-induced asthma exacerbation in 7 healthy controls and 17 (at baseline) and 18 (at day 4 post infection) people with asthma. Findings: We observed in vitro: M1-like but not M2-like or unpolarized MDM are potent producers of type I and III interferons in response to RV infection (P<0.0001), and M1-like are more resistant to RV infection (P<0.05); compared to M1-like, M2-like MDM constitutively produced higher levels of CCL22/MDC (P = 0.007) and CCL17/TARC (P<0.0001); RV-infected M1-like MDM were characterized as CD14 + CD80 + CD197 + (P = 0.002 vs M2-like, P<0.0001 vs unpolarized MDM). In vivo we found reduced percentages of M1-like CD14 + CD80 + CD197 + BAL ML in asthma during experimental RV16 infection compared to baseline (P = 0.024). Interpretation: Human M1-like BAL ML are likely important contributors to anti-viral immunity and their numbers are reduced in patients with allergic asthma during RV-induced asthma exacerbations. This mechanism may be one explanation why RV-triggered clinical and pathologic outcomes are more severe in allergic patients than in healthy subjects.
We have performed our study on a NEN-treated RB cell culture derived from a real clinical autopsy material. 3.5-year-old male donor has died of a massive complex abdominal trauma being previously RB-diagnosed with NMR and ultrasound tests, tumor located behind the eye globe equator line. This is a first report ever on magnetic isotope effects of metal ions to cause the clear anti-cancer consequences in retinoblastoma cells by depriving them of the DNA repair capabilities. Both molecular mechanism of phenomenon and its possible meaning for retinoblastoma chemotherapy are presented here.