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F T Cross

Publications and source records attributed to F T Cross.

16 recordsLinked to original sources
PubMed1992

Radon-induced deletions in human cells: role of nonhomologous strand rejoining.

Radon is a ubiquitous inhaled human carcinogen that is thought to be the largest single natural source of human exposure to radiation. We report that a freely replicating episome in human cells exposed to radon gas underwent mutagenic changes, a high proportion of which were large deletions involving many thousands of base pairs. These deletions were not randomly distributed but started and ended in defined regions as if caused by the passage of a single alpha-particle track through a coiled chromatin structure. The sizes appeared to be defined by structural features of chromatin: the minimum size was 2435 base pairs, and the maximum size was 8051 base pairs, close to the upper limit that would leave intact the plasmid sequences required for selection in bacteria. Ends were rejoined by nonhomologous recombination involving up to 6 base pairs of homology. This process may not be confined to the repair of exogenously induced double-strand breaks but may be used for rejoining free DNA ends generated by a variety of cellular processes. The mechanism of alpha-particle deletion mutagenesis may account for the high relative biological effectiveness of radon irradiation for many end points and its consequences for lung carcinogenesis.

Base Sequence↗
PubMed1992

Interlaboratory comparison of different alpha-particle and radon sources: cell survival and relative biological effectiveness.

Alpha radiation-induced cell killing was determined in four different laboratories in order to: 1) measure interlaboratory variability and 2) compare the effects of radon and radon daughter exposures with the effects of 238Pu (an often-used model for radon exposure). The results suggest that differences in handling from laboratory to laboratory can affect both low and high linear energy transfer responses and should be considered when comparing results from different laboratories.

Alpha Particles↗
PubMed1991

In vitro exposure of mammalian cells to radon: dosimetric considerations.

We have developed a model to calculate the dose to the cell nucleus in cells exposed in suspension to radon and/or radon progeny. The model addresses the influence of (1) different radiation qualities and energies in the irradiation milieu; (2) the contribution to dose from radioactivity in the medium surrounding the cell after exposure to the radon gas as well as that from excess radon progeny associated with the cell; (3) the geometry of the cell and of the radiosensitive target, the cell nucleus; (4) the intracellular localization of the radionuclides; (5) attenuation of the alpha particles by the cytoplasm; (6) the radionuclide concentrations in the medium; and (7) the length of exposure. Investigation of the influence of these various parameters was made using an irradiation system in which cells were exposed to 212Bi, which decays to stability with the emission of an alpha particle (either 6.05 or 8.78 MeV). The information from these studies was then used to develop the system further for more complex systems in which 222Rn and its progeny are present. The model takes into account the contribution of dose from different radiation sources using scintillation counts of the medium and the cells, and it is useful for calculations of dose in situations where cells are exposed in suspension culture.

Animals↗
PubMed1990

A two-mutation model for radon-induced lung tumors in rats.

The recessive oncogenesis model, according to which inactivation of both alleles of specific genes leads to cancer, has received much recent attention. A mathematical formulation of a two-mutation model for carcinogenesis, which includes the recessive oncogenesis model as a special case, was fitted to data from a large experimental study in which rats exposed to radon daughters developed malignant lung tumors. The model described the data well. The results indicate that fractionation of exposure increased the lifetime probability of tumor. Examination of the parameters of the model suggests that the effect of fractionation can be explained by the relative effects of radon daughters on the mutation rates and on the kinetics of growth of initiated cells. The first mutation rate is very strongly dependent upon the rate of exposure to radon daughters, the second mutation rate much less so, suggesting that the nature of the two mutational events is different. The model makes predictions which are testable in future experiments.

Animals↗
PubMed1989

The current approach of the ICRP Task Group for modeling doses to respiratory tract tissues.

For radiation protection purposes, the International Commission on Radiological Protection (ICRP) Task Group proposes to apportion radiation risk within the respiratory tract according to the tumor mortality rates observed in the different anatomical regions. This approach requires that doses absorbed by extrathoracic tissues must be considered, in addition to those in the lung. For the extrathoracic region, the tissues at highest potential risk are the pharyngeal parts of the nasopharynx and oropharynx and a part of the larynx. In the lung, all tissues are potentially at risk, and it is necessary to consider doses absorbed by bronchial tissues, the lung parenchyma, and lymph nodes. This paper outlines the methods proposed by the Task Group to evaluate the heterogeneous doses absorbed by sensitive cells in these tissues from radioactive decays of alpha-emitters. The objective is to evaluate doses to broad regions of the respiratory tract, where the regions are defined to reflect substantial differences in potential risk when taking into account deposition and clearance behavior. The Task Group proposes to represent the respiratory tract by three generic regions: an extrathoracic region and two thoracic regions, one clearing fast and one slowly. The models of aerosol deposition and clearance applied for each region are outlined. To illustrate the use of the model, doses are evaluated for the key cases of short-lived radionuclides and long-lived insoluble alpha-emitters and are discussed with regard to current ICRP recommendations.

Aerosols↗
PubMed1989

Risk considerations related to lung modeling.

Improved lung models provide a more accurate assessment of dose from inhalation exposures and, therefore, more accurate dose-response relationships for risk evaluation and exposure limitation. Epidemiological data for externally irradiated persons indicate that the numbers of excess respiratory tract carcinomas differ in the upper airways, bronchi, and distal lung. Neither their histogenesis and anatomical location nor their progenitor cells are known with sufficient accuracy for accurate assessment of the microdosimetry. The nuclei of sensitive cells generally can be assumed to be distributed at random in the epithelium, beneath the mucus and tips of the beating cilia and cells. In stratified epithelia, basal cells may be considered the only cells at risk. Upper-airway tumors have been observed in both therapeutically irradiated patients and in Hiroshima-Nagasaki survivors. The current International Commission on Radiological Protection Lung-Model Task Group proposes that the upper airways and lung have a similar relative risk coefficient for cancer induction. The partition of the risk weighting factor, therefore, will be proportional to the spontaneous death rate from tumors, and 80% of the weighting factor for the respiratory tract should be attributed to the lung. For Weibel lung-model branching generations 0 to 16 and 17 to 23, the Task Group proposes an 80/20 partition of the risk, i.e., 64% and 16%, respectively, of the total risk. Regarding risk in animals, recent data in rats indicate a significantly lower effectiveness for lung-cancer induction at low doses from insoluble long-lived alpha-emitters than from Rn daughters. These findings are due, in part, to the fact that different regions of the lung are irradiated. Tumors in the lymph nodes are rare in people and animals exposed to radiation. The Task Group, therefore, suggests that the total risk to the nodes cannot exceed 1/100th of the total risk to the respiratory tract, which, in turn, leads to an extremely low cancer incidence per unit dose for lymphatic tissue.

Aerosols↗
PubMed1986

Contribution of radon and radon daughters to respiratory cancer.

This article reviews studies on the contribution of radon and radon daughters to respiratory cancer and proposes recommendations for further research, particularly a national radon survey. The steady-state outdoor radon concentration averages 200 pCi/m3, and indoor levels are about 4 times higher. The primary source of radon in homes is the underlying soil; entry depends on multiple variables and reduced ventilation for energy conservation increases indoor radon levels. Occupational exposures are expressed in units of radon daughter potential energy concentration or working level (WL). Cumulative exposure is the product of the working level and the time exposed. The unit for cumulative exposure is the working level month (WLM). The occupational standard for radon exposure is 4 WLM/year, and 2 WLM/year has been suggested as a guideline for remedial action in homes. Epidemiologic studies show that miners with cumulative radon daughter exposures somewhat below 100 WLM have excess lung cancer mortality. Some 3% to 8% of miners studied have developed lung cancer attributable to radon daughters. All of the underground mining studies show an increased risk of lung cancer with radon daughter exposure. All cell types of lung cancer increased with radon exposure. If radon and smoking act in a multiplicative manner, then the risk for smokers could be 10 times that for nonsmokers. The potential risk of lung cancer appears to be between 1 and 2 per 10,000/WLM, which yields a significant number of lung cancers as some 220 million persons in the United States are exposed on average to 10 to 20 WLM/lifetime.

Carcinoma, Bronchogenic↗
PubMed1985

Estimation of health effects due to elevated radiation exposure levels in structures.

Uranium mill tailings were used as landfill for many years in the United States before the health risk associated with such use was recognized. Occupants of buildings erected on or adjacent to contaminated landfills may experience radiation exposures sufficient to warrant remedial action. Estimates of the cost-effectiveness of the remedial measures may be provided using a combination of occupancy data, appropriate risk coefficients and projected costs. This effort is in support of decisions by the U.S. Department of Energy (DOE) to conduct remedial action at such locations. The methods used in this project, with examples of their application, will be presented in this paper.

Environmental Exposure↗
PubMed1985

Health effects and risks from 222Rn in drinking water.

This paper presents an evaluation of the inhalation and ingestion doses from exposure to Rn and Rn progeny; an overview of the human and animal health-effects data; estimations of the cancer risks from Rn and Rn-progeny exposures; and suggested limits for Rn concentrations in drinking water and indoor air. We suggest that a rounded Rn-in-water concentration limit of 10,000 pCi/l can be supported by health-effects considerations alone, based on the conservative "tolerance dose" concept and other conservative assumptions regarding lung dose. A practical concentration limit (or action level) of 20,000 pCi/l has been derived by estimations of exposure distributions in the United States and in relation to current U.S. Environmental Protection Agency (EPA) standards for U-tailings-contaminated buildings. Research needed for resolution of the uncertainties in these estimates is suggested. We conclude that before a maximum contaminant level (MCL) for Rn in water can be firmly established, the broader issue of setting the MCL for Rn in indoor air must be addressed.

Air Pollutants, Occupational↗
PubMedDate not supplied

Adaptive response of human lymphocytes for the repair of radon-induced chromosomal damage.

In human lymphocytes low doses of X-rays can decrease the number of chromatid deletions induced by subsequent high doses of sparsely ionizing X-rays. Because of the concern with the carcinogenic effects of low doses of alpha-particles from radon in homes, experiments were carried out to see if low doses of X-rays could also decrease the yield of chromosomal aberrations induced by subsequent exposure to radon. Human peripheral blood lymphocytes were irradiated with low doses of X-rays (2 cGy) at 48 h of culture, exposed to radon at 72 h of culture, and analyzed for the presence of chromatid aberrations at subsequent intervals. The frequency of chromatid aberrations induced by radon alone increased with time after exposure, indicating exaggerated differences in the stage sensitivity of cell cycle stages to high-LET radiation. Furthermore, the numbers of aberrations per cell did not follow a Poisson distribution but were over dispersed, as might be expected since high-LET radiations have a high relative biological effectiveness compared with low-LET radiations. Nevertheless, lymphocytes exposed to 2 cGy of X-rays before radon exposure contained approximately one-half the number of chromatid deletions compared with lymphocytes treated with radon alone and analyzed at the same time. Thus, the putative chromosomal repair mechanism induced by low doses of sparsely ionizing radiation is also effective in reducing chromosomal aberrations induced by radon, which hitherto had been thought to be relatively independent of repair processes.

Adaptation, Physiological↗