Ever since x-rays were shown to induce mutation in Drosophila more than 70 years ago, prevailing dogma considered the genotoxic effects of ionizing radiation, such as mutations and carcinogenesis, as being due mostly to direct damage to the nucleus. Although there was indication that alpha particle traversal through cellular cytoplasm was innocuous, the full impact remained unknown. The availability of the microbeam at the Radiological Research Accelerator Facility of Columbia University made it possible to target and irradiate the cytoplasm of individual cells in a highly localized spatial region. By using dual f luorochrome dyes (Hoechst and Nile Red) to locate nucleus and cellular cytoplasm, respectively, thereby avoiding inadvertent traversal of nuclei, we show here that cytoplasmic irradiation is mutagenic at the CD59 (S1) locus of human-hamster hybrid (A L ) cells, while inf licting minimal cytotoxicity. The principal class of mutations induced are similar to those of spontaneous origin and are entirely different from those of nuclear irradiation. Furthermore, experiments with radical scavenger and inhibitor of intracellular glutathione indicated that the mutagenicity of cytoplasmic irradiation depends on generation of reactive oxygen species. These findings suggest that cytoplasm is an important target for genotoxic effects of ionizing radiation, particularly radon, the second leading cause of lung cancer in the United States. In addition, cytoplasmic traversal by alpha particles may be more dangerous than nuclear traversal, because the mutagenicity is accomplished by little or no killing of the target cells.

An Fe-Ce bimetal adsorbent was investigated with X-ray powder diffraction (XRD), transmission electron micrograph (TEM), Fourier transform infrared spectra (FTIR), and X-ray photoelectron spectroscopy (XPS) methods for a better understanding of the effect of surface properties on arsenate (As(V)) adsorption. In the adsorption test, the bimetal oxide adsorbent showed a significantly higher As-(V) adsorption capacity than the referenced Ce and Fe oxides (CeO 2 and Fe 3 O 4 ) prepared by the same procedure and some other arsenate adsorbents reported recently. XRD measurement of the adsorbent demonstrated that the phase of magnetite (Fe 3 O 4 ) disappears gradually with the increasing dosage of Ce 4+ ions until reaching a molar ratio of Ce 4+ to Fe 3+ and Fe 2+ of 0.08:0.2:0.1 (Fe-Ce08 refers to the adsorbent prepared at this ratio), and the phase of CeO 2 begins to appear following a further increase of the Ce dose. Combined with the results of TEM observation, it was assumed that a solid solution of Fe-Ce is formed following the disappearance of the magnetite phase. Occurrence of a characteristic surface hydroxyl group (M-OH, metal surface hydroxyl, 1126 cm -1 ), which showed the highest band intensity in the solid solution state, was confirmed on the bimetal oxide adsorbent by FTIR. Quantificational calculation from the XPS narrow scan results of O(1s) spectra also indicated that the formation of the bimetal Fe-Ce08 was composed of more hydroxyl (30.8%) than was the formation of CeO 2 and Fe 3 O 4 (12.6% and 19.6%). The results of adsorption tests on Fe-Ce08 at different As(V) concentrations indicated that both the integral area of the As-O band at 836 cm -1 and the As(V) adsorption capacity increased almost linearly with the decrease of the integral area of M-OH bands at 1126 cm -1 , proving that the adsorption of As(V) by Fe-Ce08 is mainly realized through the mechanism of quantitative ligand exchange. The atomic ratio of Fe on Fe-Ce08 decreased from 20.1% to 7.7% with the increase of the As atom ratio from 0 to 16% after As(V) adsorption, suggesting that As(V) adsorption might be realized through the replacement of the M-OH group of Fe (Fe-OH) with arsenate. The well splitting of three υ 3 bands at As-O band (836 cm -1 ) of FTIR and the hydroxyl ratio (1.7) of Fe-Ce08 calculated from the XPS results suggested that the diprotonated monodentate complex (SOAsO(OH) 2 ) is possibly dominant on the surface of Fe-Ce08.

The radiation-induced bystander effect is defined as ''the induction of biological effects in cells that are not directly traversed by a charged particle but are in close proximity to cells that are.'' Although these bystander effects have been demonstrated with a variety of biological endpoints in both human and rodent cell lines (as well as in 3D tissue samples), the mechanism of the phenomenon is not known. Although gap junction communication and the presence of soluble mediator(s) are both known to play important roles in the bystander response, the precise signaling molecules have yet to be identified. By using the Columbia University charged particle beam in conjunction with a strip dish design, we show here that the cyclooxygenase-2 (COX-2, also known as prostaglandin endoperoxide synthase-2) signaling cascade plays an essential role in the bystander process. Treatment of bystander cells with NS-398, which suppresses COX-2 activity, significantly reduced the bystander effect. Because the critical event of the COX-2 signaling is the activation of the mitogen-activated protein kinase pathways, our finding that inhibition of the extracellular signal-related kinase phosphorylation suppressed bystander response further confirmed the important role of mitogen-activated protein kinase signaling cascade in the bystander process. These results provide evidence that the COX-2-related pathway, which is essential in mediating cellular inflammatory response, is the critical signaling link for the bystander phenomenon.