Long-term genomic instability in human lymphocytes induced by single-particle irradiation

Recent evidence suggests that genomic instability, which is an important step in carcinogenesis, may be important in the effectiveness of radiation as a carcinogen, particularly for high-LET radiations. Understanding the biological effects underpinning the risks associated with low doses of densely ionizing radiations is complicated in experimental systems by the Poisson distribution of particles that ran be delivered, In this study, we report an approach to determine the effect of the lowest possible cellular radiation dose of densely ionizing at particles, that of a single particle traversal. Using microbeam technology and an approach for immobilizing human T-lymphocytes, we have measured the effects of single alpha -particle traversals on the surviving progeny of cells. A significant increase in the proportion of aberrant cells is observed 12-13 population doublings after exposure, with a high level of chromatid-type aberrations, indicative of an instability phenotype, These data suggest that instability may be important in situations where even a single particle traverses human cells. (C) 2001 by Radiation Research Society.

Local DNA damage by proton microbeam irradiation induces poly(ADP-ribose) synthesis in mammalian cells

Cellular recovery from ionizing radiation (IR)-induced damage involves poly(ADP-ribose) polymerase (PARP-1 and PARP-2) activity, resulting in the induction of a signalling network responsible for the maintenance of genomic integrity. In the present work, a charged particle microbeam delivering 3.2 MeV protons from a Van de Graaff accelerator has been used to locally irradiate mammalian cells. We show the immediate response of PARPs to local irradiation, concomitant with the recruitment of ATM and Rad51 at sites of DNA damage, both proteins being involved in DNA strand break repair. We found a co-localization but no connection between two DNA damage-dependent post-translational modifications, namely poly(ADP-ribosyl)ation of nuclear proteins and phosphorylation of histone H2AX. Both of them, however, should be considered and used as bona fide immediate sensitive markers of IR damage in living cells. This technique thus provides a powerful approach aimed at understanding the interactions between the signals originating from sites of DNA damage and the subsequent activation of DNA strand break repair mechanisms.

Effective suppression of bystander effects by DMSO treatment of irradiated CHO cells

Evidence is accumulating that irradiated cells produce some signals which interact with non-exposed cells in the same population via a bystander effect. Here, we examined whether DMSO is effective in suppressing radiation induced bystander effects in CHO and repair deficient xrs5 cells. When 1 Gy-irradiated CHO cells were treated with 0.5% DMSO for 1 hr before irradiation, the induction of micronuclei in irradiated cells was suppressed to 80% of that in non-treated irradiated cells. The suppressive effect of DMSO on the formation of bystander signals was examined and the results demonstrated that 0.5% DMSO treatment of irradiated cells completely suppressed the induction of micronuclei by the bystander effect in non-irradiated cells. It is suggested that irradiated cells ceased signal formation for bystander effects by the action of DMSO. To determine the involvement of reactive oxygen species on the formation of bystander signals, we examined oxidative stress levels using the DCFH staining method in irradiated populations. The results showed that the treatment of irradiated cells with 0.5% DMSO did not suppress oxidative stress levels. These results suggest that the prevention of oxidative stress is independent of the suppressive effect of DMSO on the formation of the bystander signal in irradiated cells. It is suggested that increased ROS in irradiated cells is not a substantial trigger of a bystander signal.

Biological Cell Irradiation At Ultrahigh Dose Rate Employing Laser Driven Protons

The ultrashort duration of laser-driven multi-MeV ion bursts offers the possibility of radiobiological studies at extremely high dose rates. Employing the TARANIS Terawatt laser at Queen's University, the effect of proton irradiation at MeV-range energies on live cells has been investigated at dose rates exceeding 10⁹Gy/s as a single exposure. A clonogenic assay showed consistent lethal effects on V-79 live cells, which, even at these dose rates, appear to be in line with previously published results employing conventional sources. A Relative Biological Effectiveness (RBE) of 1.4±0.2 at 10% survival is estimated from a comparison with a 225 kVp X-ray source. 

Diagnosis of common bile duct stones by intravenous cholangiography:prediction by ultrasound and liver function tests compared with endoscopic retrograde cholangiography

Routine intravenous cholangiography using the safer contrast medium, meglumine iotroxate, may be a useful investigation prior to laparoscopic cholecystectomy for the detection of suspected common bile duct stones. We compared this with endoscopic cholangiography.