Extension of the RADTriage Colorimetric Dosimeter to Low-Dose Gamma-Ray Exposure Using Scanning Densitometry.

There is a need for an instantly indicating, easy-to-read, and inexpensive ionizing radiation dosimeter for first responders and members of the general public. One commercially available option is the RADTriage50 TM colorimetric dosimeter. However, existing literature has not adequately addressed the accuracy of RADTriage50 dosimeters at low doses of ionizing radiation (<50 mSv) or the need for methods to quantitatively read the RADTriage50 dosimeters after they are exposed.

Predicting the Public Health Consequences of a Nuclear Terrorism Attack: Drawing on The Experiences of Hiroshima and Fukushima.

The increasing threat of nuclear terrorism warrants consideration of the health consequences of a terrorist incident should preventive measures fail. Although there has not yet been a nuclear terrorist attack of any kind, experiences with the aftermath of the bombing of Hiroshima and the core meltdowns at Fukushima can provide useful insight and allow some inferences to be made regarding the types of casualties that might be sustained and the rescue efforts that might be required. There are many parallels between the events at Hiroshima and what might be expected from an improvised nuclear device, and there are parallels between the radioactivity released to the environment at Fukushima and the aftermath of a radiological dispersal device attack.

Dose coefficients for ICRP reference pediatric phantoms exposed to idealised external gamma fields.

Organ and effective dose coefficients have been calculated for the International Commission on Radiological Protection (ICRP) reference pediatric phantoms externally exposed to mono-energetic photon radiation (x- and gamma-rays) from 0.01 to 20 MeV. Calculations used Monte Carlo radiation transport techniques.

The New "Normal": Stakeholders and Radiation Protection Limits in a Post-9/11 World.

With the recent upsurge in worldwide terrorism, the prospects for a radiation terrorism event have greatly increased. Current recommendations regarding recovery from such an event specify that decisions about the extent of radiological cleanup will be dependent upon stakeholder acceptance of the risk levels. The case is made here that stakeholders are currently not prepared to make decisions collectively about the acceptability of risk levels and will be even less capable during the aftermath of an attack when a consensus among stakeholders is unlikely to be achieved.

Mitigating the risk of radiation-induced cancers: limitations and paradigms in drug development.

The United States radiation medical countermeasures (MCM) programme for radiological and nuclear incidents has been focusing on developing mitigators for the acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE), and biodosimetry technologies to provide radiation dose assessments for guiding treatment. Because a nuclear accident or terrorist incident could potentially expose a large number of people to low to moderate doses of ionising radiation, and thus increase their excess lifetime cancer risk, there is an interest in developing mitigators for this purpose. This article discusses the current status, issues, and challenges regarding development of mitigators against radiation-induced cancers.

DNA repair gene variants in relation to overall cancer risk: a population-based study.

The hypothesis that germ-line polymorphisms in DNA repair genes influence cancer risk has previously been tested primarily on a cancer site-specific basis. The purpose of this study was to test the hypothesis that DNA repair gene allelic variants contribute to globally elevated cancer risk by measuring associations with risk of all cancers that occurred within a population-based cohort. In the CLUE II cohort study established in 1989 in Washington County, MD, this study was comprised of all 3619 cancer cases ascertained through 2007 compared with a sample of 2296 with no cancer.

A population-based study of hedgehog pathway gene variants in relation to the dual risk of basal cell carcinoma plus another cancer.

Introduction: A personal history of basal cell carcinoma (BCC) is associated with increased risk of other malignancies, but the reason is unknown. The hedgehog pathway is critical to the etiology of BCC, and is also believed to contribute to susceptibility to other cancers. This study tested the hypothesis that hedgehog pathway and pathway-related gene variants contribute to the increased risk of subsequent cancers among those with a history of BCC.

A population-based study of DNA repair gene variants in relation to non-melanoma skin cancer as a marker of a cancer-prone phenotype.

For unknown reasons, non-melanoma skin cancer (NMSC) is associated with increased risk of other malignancies. Focusing solely on DNA repair or DNA repair-related genes, this study tested the hypothesis that DNA repair gene variants contribute to the increased cancer risk associated with a personal history of NMSC. From the parent CLUE II cohort study, established in 1989 in Washington County, MD, the study consisted of a cancer-free control group (n 5 2296) compared with three mutually exclusive groups of cancer cases ascertained through 2007: (i) Other (non-NMSC) cancer only (n 5 2349); (ii) NMSC only (n 5 694) and (iii) NMSC plus other cancer (n 5 577).

A community-based study of nucleotide excision repair polymorphisms in relation to the risk of non-melanoma skin cancer.

Nucleotide excision repair (NER) is responsible for protecting DNA in skin cells against UVR-induced damage. Using a candidate pathway approach, a matched case-control study nested within a prospective, community-based cohort was carried out to test the hypothesis that single-nucleotide polymorphisms (SNPs) in NER genes are associated with susceptibility to non-melanoma skin cancer (NMSC). Histologically confirmed cases of NMSC (n=900) were matched to controls (n=900) on the basis of age, gender, and skin type.

Elevated Epstein-Barr virus seroreactivity among unaffected members of families with nasopharyngeal carcinoma.

Serum antibodies to Epstein-Barr virus (EBV) antigens can be used to predict the risk of nasopharyngeal carcinoma (NPC). To investigate whether EBV seropositivity rates were higher among healthy family members from multiplex and sporadic families with NPC (i.e.

Human genetic variants of homologous recombination repair genes first found to be associated with Epstein-Barr virus antibody titers in healthy Cantonese.

Epstein-Barr virus (EBV) infection is a major risk factor for nasopharyngeal carcinoma (NPC). Despite high prevalence of infection among the general population worldwide, only a small proportion of infected individuals presents with seropositivity for EBV-specific IgA antibodies. This seropositive subgroup of EBV carriers has an elevated cumulative risk for NPC during their lifetime.

Phosphorylation of histone H2A.X as an early marker of neuronal endangerment following seizures in the adult rat brain.

The phosphorylated form of histone H2A.X (γ-H2AX) is a well documented early, sensitive, and selective marker of DNA double-strand breaks (DSBs). Previously, we found that excessive glutamatergic activity increased γ-H2AX in neurons in vitro.

Comprehensive pathway-based association study of DNA repair gene variants and the risk of nasopharyngeal carcinoma.

DNA repair plays a central role in protecting against environmental carcinogenesis, and genetic variants of DNA repair genes have been reported to be associated with several human malignancies. To assess whether DNA gene variants were associated with nasopharyngeal carcinoma (NPC) risk, a candidate gene association study was conducted among the Cantonese population within the Guangdong Province, China, the ethnic group with the highest risk for NPC. A 2-stage study design was utilized.

Hypothesis-driven candidate gene association studies: practical design and analytical considerations.

Candidate gene association studies (CGAS) are a useful epidemiologic approach to drawing inferences about relations between genes and disease, especially when experimental data support the involvement of specific biochemical pathways. The value of CGAS is apparent when allele frequencies are low, effect sizes are small, or the study population is limited or unique. CGAS is also valuable for validating previous reports of genetic associations with disease in different populations.

The association between skin characteristics and skin cancer prevention behaviors.

Background: Behaviors such as sunscreen use and wearing sun-protective clothing are thought to prevent certain types of skin cancer and precancerous lesions, but few studies have examined differences in these prevention behaviors by skin type.

Methods: We carried out a cross-sectional study (n = 6,858) nested within a community-based prospective cohort in Washington County, Maryland. We measured the associations between skin type, complexion, freckling, and eye color, and sunscreen and sun-protective clothing use.

Genome-wide association study reveals multiple nasopharyngeal carcinoma-associated loci within the HLA region at chromosome 6p21.3.

Nasopharyngeal carcinoma (NPC) is a multifactorial malignancy closely associated with genetic factors and Epstein-Barr virus infection. To identify the common genetic variants linked to NPC susceptibility, we conducted a genome-wide association study (GWAS) in 277 NPC patients and 285 healthy controls within the Taiwanese population, analyzing 480,365 single-nucleotide polymorphisms (SNPs). Twelve statistically significant SNPs were identified and mapped to chromosome 6p21.

Binding kinetics and activity of human poly(ADP-ribose) polymerase-1 on oligo-deoxyribonucleotide substrates.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a mammalian enzyme that attaches long branching chains of ADP-ribose to specific nuclear proteins, including itself. Because its activity in vitro is dependent upon interaction with broken DNA, it has been postulated that PARP-1 plays an important role in DNA strand-break repair in vivo. The exact mechanism of binding to DNA and the structural determinants of binding remain to be defined, but regions of transition from single-stranded to double-strandedness may be important recognition sites.

Enhancing radiosensitivity: targeting the DNA repair pathways.

Radiotherapy is very effective in local control of cancerous tumors, but its curative potential is often limited by intrinsic radioresistance of the tumor cells. Since DNA repair pathways remove radiation-induced DNA lesions and protect cells from lethality, these pathways represent potential therapeutic targets to radiosensitize tumors. In order to achieve a therapeutic gain, however, there must be a differential between tumor and normal cells that can be exploited to preferentially target the DNA repair of the tumor, while sparing surrounding normal tissues, and this has represented a significant challenge to progress.

DNA repair gene variants associated with benign breast disease in high cancer risk women.

Benign breast disease (BBD) is a risk factor for breast cancer and may have a heritable component. Deficient DNA repair has been implicated in breast cancer etiology and may exert its effect before BBD, a known precursor. The association between allelic variants in DNA repair genes and BBD was examined in a cohort of women in Washington County, Maryland.

Nonmelanoma skin cancer and risk for subsequent malignancy.

Background: Individuals with a personal history of nonmelanoma skin cancer (NMSC) may have an increased risk of subsequent noncutaneous malignancies. To test this hypothesis, we carried out a community-based, prospective cohort study.

Methods: In the CLUE (Give Us a Clue to Cancer and Heart Disease) II cohort, which was established in Washington County, MD, in 1989, the risk of new malignancies was compared among individuals with (n = 769) and without (n = 18,405) a personal history of NMSC (total n = 19,174) during a 16-year follow-up period.

Chemosensitization and radiosensitization of human lung and colon cancers by antimitotic agent, ABT-751, in athymic murine xenograft models of subcutaneous tumor growth.

Purpose: ABT-751 is an orally active antimitotic agent that is currently in Phase II clinical trials. This agent binds to the colchicine site on ss-tubulin and inhibits polymerization of microtubules. This disruption of microtubule dynamics leads to a block in the cell cycle at the G2/M phase, and promotes apoptosis.

Rapid phosphorylation of histone H2A.X following ionotropic glutamate receptor activation.

Excessive activation of ionotropic glutamate receptors increases oxidative stress, contributing to the neuronal death observed following neurological insults such as ischemia and seizures. Post-translational histone modifications may be key mediators in the detection and repair of damage resulting from oxidative stress, including DNA damage, and may thus affect neuronal survival in the aftermath of insults characterized by excessive glutamate release. In non-neuronal cells, phosphorylation of histone variant H2A.