Calculation of Heavy Ion Inactivation and Mutation Rates in Radial Dose Model of Track Structure

In the track structure model, the inactivation cross section is found by summing an inactivation probability over all impact parameters from the ion to the sensitive sites within the cell nucleus. The inactivation probability is evaluated by using the dose response of the system to gamma rays and the radial dose of the ions and may be equal to unity at small impact parameters. We apply the track structure model to recent data with heavy ion beams irradiating biological samples of E. Coli, Bacillus Subtilis spores, and Chinese hamster (V79) cells. Heavy ions have observed cross sections for inactivation that approach and sometimes exceed the geometric size of the cell nucleus in mammalian cells. We show how the effects of inactivation may be taken into account in the evaluation of the mutation cross sections from heavy ions in the track structure model through correlation of sites for gene mutation and cell inactivation. The model is fit to available data for HPRT (hypoxanthine guanine phosphoribosyl transferase) mutations in Chinese hamster cells, and good agreement is found. The resulting calculations qualitatively show that mutation cross sections for heavy ions display minima at velocities where inactivation cross sections display maxima. Also, calculations show the high probability for mutation by relativistic ions due to the radial extension of the ion track from delta rays in agreement with the microlesion concept. The effects of inactivation on mutation rates make it very unlikely that a single parameter such as LET (linear energy transfer) or Z*2/ β2&#;(where Z*is effective charge number and β is ion velocity) can be used to specify radiation quality for heavy ion bombardment

Calculation of Heavy Ion Inactivation and Mutation Rates in Radial Dose Model of Track Structure

In the track structure model, the inactivation cross section is found by summing an inactivation probability over all impact parameters from the ion to the sensitive sites within the cell nucleus. The inactivation probability is evaluated by using the dose response of the system to gamma rays and the radial dose of the ions and may be equal to unity at small impact parameters. We apply the track structure model to recent data with heavy ion beams irradiating biological samples of E. Coli, B. Subtilis spores, and Chinese hamster (V79) cells. Heavy ions have observed cross sections for inactivation that approach and sometimes exceed the geometric size of the cell nucleus. We show how the effects of inactivation may be taken into account in the evaluation of the mutation cross sections in the track structure model through correlation of sites for gene mutation and cell inactivation. The model is fit to available data for HPRT (hypoxanthine guanine phosphoribosyl transferase) mutations in V79 cells, and good agreement is found. Calculations show the high probability for mutation by relativistic ions due to the radial extension of ions track from delta rays. The effects of inactivation on mutation rates make it very unlikely that a single parameter such as LET (linear energy transfer) can be used to specify radiation quality for heavy ion bombardment

Calculation of Heavy Ion Inactivation and Mutation Rates in Radial Dose Model of Track Structure

In the track structure model, the inactivation cross section is found by summing an inactivation probability over all impact parameters from the ion to the sensitive sites within the cell nucleus. The inactivation probability is evaluated by using the dose response of the system to gamma rays and the radial dose of the ions and may be equal to unity at small impact parameters. We apply the track structure model to recent data with heavy ion beams irradiating biological samples of E. Coli, Bacillus Subtilis spores, and Chinese hamster (V79) cells. Heavy ions have observed cross sections for inactivation that approach and sometimes exceed the geometric size of the cell nucleus in mammalian cells. We show how the effects of inactivation may be taken into account in the evaluation of the mutation cross sections from heavy ions in the track structure model through correlation of sites for gene mutation and cell inactivation. The model is fit to available data for HPRT (hypoxanthine guanine phosphoribosyl transferase) mutations in Chinese hamster cells, and good agreement is found. The resulting calculations qualitatively show that mutation cross sections for heavy ions display minima at velocities where inactivation cross sections display maxima. Also, calculations show the high probability for mutation by relativistic ions due to the radial extension of the ion track from delta rays in agreement with the microlesion concept. The effects of inactivation on mutation rates make it very unlikely that a single parameter such as LET (linear energy transfer) or Z*2/ β2&#;(where Z*is effective charge number and β is ion velocity) can be used to specify radiation quality for heavy ion bombardment

Differences in the Tumor Microenvironment between African-American and European-American Breast Cancer Patients

Background: African-American breast cancer patients experience higher mortality rates than European-American patients despite having a lower incidence of the disease. We tested the hypothesis that intrinsic differences in the tumor biology may contribute to this cancer health disparity. Methods and Results: Using laser capture microdissection, we examined genome-wide mRNA expression specific to tumor epithelium and tumor stroma in 18 African-American and 17 European-American patients. Numerous genes were differentially expressed between these two patient groups and a two-gene signature in the tumor epithelium distinguished between them. To identify the biological processes in tumors that are different by race/ethnicity, Gene Ontology and disease association analyses were performed. Several biological processes were identified which may contribute to enhanced disease aggressiveness in African-American patients, including angiogenesis and chemotaxis. African-American tumors also contained a prominent interferon signature. The role of angiogenesis in the tumor biology of African-American

Comparison of dose and risk estimates between ISS Partner Agencies for a 30-day lunar mission

The International Partner Agencies of the International Space Station (ISS) present a comparison of the ionizing radiation absorbed dose and risk quantities used to characterize example missions in lunar space. This effort builds on previous collaborative work that characterizes radiation environments in space to support radiation protection for human spaceflight on ISS in low-Earth orbit (LEO) and exploration missions beyond (BLEO). A “shielded” ubiquitous galactic cosmic radiation (GCR) environment combined with––and separate from––the transient challenge of a solar particle event (SPE) was modelled for a simulated 30-day mission period. Simple geometries of relatively thin and uniform shields were chosen to represent the space vehicle and other available shielding, and male or female phantoms were used to represent the body’s self-shielding. Absorbed dose in organs and tissues and the effective dose were calculated for males and females. Risk parameters for cancer and other outcomes are presented for selected organs. The results of this intracomparison between ISS Partner Agencies itself provide insights to the level of agreement with which space agencies can perform organ dosimetry and calculate effective dose. This work was performed in collaboration with the advisory and guidance efforts of the International Commission on Radiological Protection (ICRP) Task Group 115 and will be presented in an ICRP Repor

Establishing a consortium for the study of rare diseases: The Urea Cycle Disorders Consortium

The Urea Cycle Disorders Consortium (UCDC) was created as part of a larger network established by the National Institutes of Health to study rare diseases. This paper reviews the UCDC's accomplishments over the first 6years, including how the Consortium was developed and organized, clinical research studies initiated, and the importance of creating partnerships with patient advocacy groups, philanthropic foundations and biotech and pharmaceutical companies