Antone L. Brooks

Current status of cytogenetic procedures to detect and quantify previous exposures to radiation

The estimation of the magnitude of a dose of ionizing radiation to which an individual has been exposed (or of the plausibility of an alleged exposure) from chromosomal aberration frequencies determined in peripheral blood lymphocyte cultures is a well-established methodology, having first been employed over 25 years ago. The cytogenetics working group has reviewed the accumulated data and the possible applicability of the technique to the determination of radiation doses to which American veterans might have been exposed as participants in nuclear weapons tests in the continental U.S.A. or the Pacific Atolls during the late 1940s and 1950s or as members of the Occupation Forces entering Hiroshima or Nagasaki shortly after the nuclear detonations there. The working group believes that with prompt peripheral blood sampling, external doses to individuals of the order of about 10 rad (or less if the exposure was to high-LET radiation) can accurately be detected and measured. It also believes that exposures of populations to doses of the order of maximum permissible occupational exposures can also be detected (but only in populations; not in an individual). Large exposures of populations can also be detected even several decades after their exposure, but only in the case of populations, and of large doses (of the order of 100 to several hundred rad). The working group does not believe that cytogenetic measurements can detect internal doses from fallout radionuclides in individuals unless these are very large. The working group has approached the problem of detection of small doses (less than or equal to 10 or so rad) sampled decades after the exposure of individuals by using a Bayesian statistical approach. Only a preliminary evaluation of this approach was possible, but it is clear that it could provide a formal statement of the likelihood that any given observation of a particular number of chromosomal aberrations in a sample of any particular number of lymphocytes actually indicates an exposure to any given dose of radiation. It is also clear that aberration frequencies (and consequently doses) would have to be quite high before much confidence could be given to either exposure or dose estimation by this method, given the approximately 3 decades of elapsed time between the exposures and any future blood sampling.(ABSTRACT TRUNCATED AT 400 WORDS)

The role of dose rate in radiation cancer risk: evaluating the effect of dose rate at the molecular, cellular and tissue levels using key events in critical pathways following exposure to low LET radiation

Abstract Purpose: This review evaluates the role of dose rate on cell and molecular responses. It focuses on the influence of dose rate on key events in critical pathways in the development of cancer. This approach is similar to that used by the U.S. EPA and others to evaluate risk from chemicals. It provides a mechanistic method to account for the influence of the dose rate from low-LET radiation, especially in the low-dose region on cancer risk assessment. Molecular, cellular, and tissues changes are observed in many key events and change as a function of dose rate. The magnitude and direction of change can be used to help establish an appropriate dose rate effectiveness factor (DREF). Conclusions: Extensive data on key events suggest that exposure to low dose-rates are less effective in producing changes than high dose rates. Most of these data at the molecular and cellular level support a large (2–30) DREF. In addition, some evidence suggests that doses delivered at a low dose rate decrease damage to levels below that observed in the controls. However, there are some data human and mechanistic data that support a dose-rate effectiveness factor of 1. In summary, a review of the available molecular, cellular and tissue data indicates that not only is dose rate an important variable in understanding radiation risk but it also supports the selection of a DREF greater than one as currently recommended by ICRP (2007) and BEIR VII (NRC/NAS 2006).

Induction of micronuclei in respiratory tract following radon inhalation

Male Wistar rats were exposed to radon and its progeny (0.0, 60, 262 and 564 working level months, WLM), and the frequency of micronuclei was determined in deep lung fibroblasts, and deep lung, trachea and nasal epithelial cells with slopes of 0.28, 0.67, 0.34 and 0.11 micronuclei/1000 binucleated cells/WLM respectively. Micronuclei in deep lung fibroblasts, isolated and cultured using two methods and media, demonstrated no differences in slopes. Biological damage was used as a biodosimeter to calculate the relationship between dosimetric units: alpha particle traversals or nuclear hits, dose in mGy and exposure in WLM. The estimated number of nuclear alpha traversals/Gy was 6.3. Radon exposure to 170 WLM resulted in the same frequency of micronuclei in deep lung epithelial cells as produced by one alpha hit/cell nucleus. Absorbed dose/unit of exposure (mGy/WLM) was estimated assuming the damage was related to absorbed dose or to changes in cell sensitivity and ranged from 1.13 to 1.34 for deep lung epithelial cells, 0.47 to 1.09 for deep lung fibroblasts, 0.34 to 0.67 for tracheal epithelial cells and 0.18 to 0.33 for nasal epithelial cells. Biological dosimetry can be used to relate exposure to damage, compare dosimetric units and validate physical dosimetry models. This approach can be applied to any inhaled material capable of producing biological damage.

Advances in Radiation Biology: Effect on Nuclear Medicine

Over the past 15 years and more, extensive research has been conducted on the responses of biological systems to radiation delivered at a low dose or low dose rate. This research has demonstrated that the molecular-, cellular-, and tissue-level responses are different following low doses than those observed after a single short-term high-dose radiation exposure. Following low-dose exposure, 3 unique responses were observed, these included bystander effects, adaptive protective responses, and genomic instability. Research on the mechanisms of action for each of these observations demonstrates that the molecular and cellular processes activated by low doses of radiation are often related to protective responses, whereas high-dose responses are often associated with extensive damage such as cell killing, tissue disruption, and inflammatory diseases. Thus, the mechanisms of action are unique for low-dose radiation exposure. When the dose is delivered at a low dose rate, the responses typically differ at all levels of biological organization. These data suggest that there must be a dose rate effectiveness factor that is greater than 1 and that the risk following low-dose rate exposure is likely less than that for single short-term exposures. All these observations indicate that using the linear no-threshold model for radiation protection purposes is conservative. Low-dose research therefore supports the current standards and practices. When a nuclear medical procedure is justified, it should be carried out with optimization (lowest radiation dose commensurate with diagnostic or therapeutic outcome).

Human lung cancer risk from radon: Influence from bystander and adaptive response non-linear dose response effects

Th is book provides a good update and review of the literature on the lung cancer risks induced by radon exposure. It demonstrates that there has been extensive literature published on these eff ects since the publication of the Biological Eff ects of Ionizing Radiation VI (BEIR VI) report Health eff ects of exposure to radon . Th e book has focused on two new paradigms in radiation biology that were not well recognized at the time BEIR VI was written. Th ese observations are the ‘ Bystander eff ects ’ and ‘ Adaptive responses ’. Dr Leonard uses his expertise in microdose analytical techniques to evaluate how each of these processes could impact the shape of the dose-response relationships for radon-induced lung cancer. He also provides an interesting mix of cell and molecular studies, experimental animal studies and epidemiological studies to estimate the shape of the dose-response relationship for radon in the low dose region. Th e book contains a useful discussion on the background and development of the Linear No-Th reshold hypothesis (LNTH). After presenting the evidence for the new biology, Dr Leonard concludes that:

The influence of changing dose rate patterns from inhaled beta-gamma emitting radionuclide on lung cancer

Abstract Purpose: Dose and dose rate are both appropriate for estimating risk from internally deposited radioactive materials. We investigated the role of dose rate on lung cancer induction in Beagle dogs following a single inhalation of strontium-90 (90Sr), cerium-144 (144Ce), yttrium-91 (91Y), or yttrium-90 (90Y). As retention of the radionuclide is dependent on biological clearance and physical half-life a representative quantity to describe this complex changing dose rate is needed. Materials and methods: Data were obtained from Beagle dog experiments from the Inhalation Toxicology Research Institute. The authors selected the dose rate at the effective half-life of each radionuclide (DRef). Results: Dogs exposed to DRef (1–100u2009Gy/day) died within the first year after exposure from acute lung disease. Dogs exposed at lower DRef (0.1–10u2009Gy/day) died of lung cancer. As DRef decreased further (<0.1u2009Gy/day 90Sr, <0.5u2009Gy/day 144Ce, <0.9u2009Gy/day 91Y, <8u2009Gy/day 90Y), survival and lung cancer frequency were not significantly different from control dogs. Conclusion: Radiation exposures resulting from inhalation of beta-gamma emitting radionuclides that decay at different rates based on their effective half-life, leading to different rates of decrease in dose rate and cumulative dose, is less effective in causing cancer than acute low linear energy transfer exposures of the lung.

The legacy of William Morgan: The PNNL years

My friendship with William F. (Bill) Morgan started in the late 970s. I was working as a technical representative at the Atomic nergy Commission in Washington D.C. and was involved in a eview of Sheldon Wolff’s laboratory at University of California, San rancisco. Bill had just joined the Wolff group as a post-doctoral ellow; he was working on radiation-induced chromosome aberraions in humans. Our review team gave the laboratory very good arks, but when the funding decisions were announced, it was arked for closure – the mysterious workings of the government. n later years, Bill was always quick to remind me that I had helped o shut down his research program! However, Bill was a very prouctive scientist right from the start and his research moved him uickly along the path to success.