No abstract

Combination of interferon-gamma (IFN-gamma) with radiation, or chemotherapeutic agents, produces different kind of modulatory effects, depending on the cell types and experimental conditions. The objective of the present study was verify the influence of IFN-gamma on the induction of apoptosis by gamma-radiation. Experiments were carried out on human fibroblast cell lines: VH-25 (primary), MRC-5, and AT-5BIVA (SV40-transformed). Exponentially growing cells were irradiated and exposed to IFN-gamma (1,000, 2,000, and 3,000 UI/mL) until in situ cell staining performed at 6, 24, and 48 h. Induction of apoptosis by ionising radiation was not verified in primary VH-25 cells. A significant increase in the frequencies of apoptotic cells was observed in SV-40-transformed cells lines, MRC-5, and AT-5BIVA fibroblasts, which were irradiated with 1.0 Gy, but the frequencies of necrotic cells were similar to the control levels. In MRC-5 cells, combined treatments with radiation and IFN-gamma induced a statistically significant reduction in the frequencies of apoptotic cells detected at 24 and 48 h after cell irradiation, while for AT cells the interaction effect (reduction of apoptosis frequency) was significant even at earlier time collection (6 h) after gamma-irradiation, and higher when compared to MRC-5 cells. The present study demonstrated that IFN-gamma showed an anti-apoptotic activity in SV40-transformed fibroblasts, normal and AT cells, which were irradiated with gamma-rays, thus indicating a mechanism dependent on the cellular type.

Experiments with novobiocin (NB) post-treatment were performed to verify its effect on the frequencies of micronuclei (MN) and chromosomal aberrations (CA) induced by γ-irradiation (0.75, 1.5 and 3.0 Gy) in human lymphocytes at G 0 -phase. The frequencies of MN significantly decreased by 44 and 50%, for the treatment with NB 50 µg/ml (30-min pulse) after radiation doses of 1.5 and 3.0 Gy, respectively. However, CA frequencies were not significantly affected. No significant effect on CA was observed when lymphocyte cultures were exposed to a single dose of 2.0 Gy at the G 0 -phase and posttreated with 25 µg/ml NB for three hours either immediately after irradiation (G 0 -phase) or after 24 h (S-phase). The significant suppressive effect of NB on MN frequencies supports the hypothesis that NB interaction with chromatin increases access to DNA repair enzymes.

IntroductionMicrochimeric male fetal cells (MFCs) have been associated with systemic lupus erythematosus, and published studies have further correlated MFC with lupus nephritis (LN). In the present study, we evaluated the frequency of MFC in the renal tissue of patients with LN.MethodsTwenty-seven renal biopsies were evaluated: Fourteen were from women with clinical and laboratory findings of LN, and thirteen were from controls. Genomic DNA was extracted from kidney biopsies, and the male fetal DNA was quantified using real-time quantitative polymerase chain reactions for the detection of specific Y chromosome sequences.ResultsMFCs were detected in 9 (64%) of 14 of patients with LN, whereas no MFCs were found in the control group (P = 0.0006). No differences in pregnancy history were found between patients with LN and the control group. Significantly higher amounts of MFCs were found in patients with LN with serum creatinine ≤1.5 mg/dl. Furthermore, women with MFCs had significantly better renal function at the time of biopsy (P = 0.03). In contrast, patients with LN without MFCs presented with more severe forms of glomerulonephritis (World Health Organization class IV = 60% and class V = 40%).ConclusionsOur data indicate a high prevalence of MFCs in renal biopsy specimens from women with LN, suggesting a role for MFCs in the etiology of LN. The present report also provides some evidence that MFCs could have a beneficial effect in this disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0615-4) contains supplementary material, which is available to authorized users.