This report summarizes progress in OHER biological research and general life sciences research programs conducted at PNL in FY 1991. The research develops the knowledge and scientific principles necessary to identify, understand, and anticipate the long-term health consequences of energy-related radiation and chemicals. Our continuing emphasis is to decrease the uncertainty of health risk estimates from existing and newly developed energy-related technologies through an increased understanding of the ways in which radiation and chemicals cause biological damage. The sequence of this report of PNL research reflects the OHER programmatic structure. The first section, Biological Research, contains reports of biological research in laboratory animals and in vitro cell systems, including research with radionuclides and chemicals. The next section, General Life Sciences Research, reports research conducted for the OHER human genome research program. Biological Research Lifespan studies in beagles with inhaled 239pu(NO3)4were in the 14th postexposure year. Thus far, 28 of 96 exposed clogs had bone tumors, 31 had lung tumors, and 9 had intrahepatic bile duct tumors. Because lung tumors were the primary plutonium exposure-related cause of death in the 239puO2-exposed dogs (51 of 116 dogs), four methods for calculating radiation close to the lungs were compared to evaluate uncertainties in radiation dose estimates. Comparisons of mean accumulative average radiation dose to the lungs were not statistically different among the four different methods, and the fraction of dogs with lung tumors for the four highest dose-range groups was similar for each method of dose calculation. Other plutonium exposure-related effects included sclerosis of the tracheobronchial lymph nodes, lymphopenia, focal radiation pneumonitis, focal dystrophic osteolytic lesions in bone, adenomatous hyperplasia of the liver, and serum chemistry indicating liver damages. General Life Sciences Research PNL is developing a computer information system to graphically display and manipulate the vast amounts of information about the human genome. The user interface, named GnomeView, provides researchers with graphical representations of chromosomes, genetic and physical maps, and DNA sequences. The architecture of the GnomeView interface has been implemented. The test set of maps for superoxide dismutase as abstracted earlier manually from Human Genome Mapping Library, GenBank, and the literature have been, for the most part, supplemented with direct access capabilities to resident abstractions of GenBank and Genome Data Base. PNL biomedical research is an interdisciplinary effort requiring scientific contributions from many research departments at PNL.

This report summarizes proE _.;s in OHER biological research and general life sciences research programs conducted at PNL in FY 1992. The research develops the knowledge and fundamental principles necessary to identify, understand, and anticipate the long-term health consequences of energyrelated radiation and chemicals. Our continuing emphasis is to decrease the uncertainty of health risk estimates from energy-related technologies through an increased understanding of the ways in which radiation and chemicals cause biological damage. The sequence of this report of PNL research reflects the OHER programmatic structure. The first section, Biological Research, contains reports of biological research in laboratory animals and in vitro cell systems, including research with radiation, radionuclides, and chemicals. The next section, General Life Sciences Research, reports research conducted for the OHER human genome research program. Biological Research Lifespan studies in beagles with inhaled 239pu(NO3)4were in the 15th postexposure year. Ali 105 plutonium-exposed dogs are dead; 28 dogs had bone tumors, 34 had lung tumors, and 14 had liver tumors. Bone or lungtumors were also the primary plutonium-exposure-related causes of death in beagles with inhaled 238puO2initial lung depositions (ILD) _.0.67kBq. Six of the dogs had liver tumors; however, liver tumors were the cause of death in only 1 dog. Although liver tumors were not a primary cause of death, chronic increased levels of serum alanine aminotransferase (ALT),indicating liver damage, were observed in dose-level groups with ILD :.2.9 kBq 9 years after exposure, 4 years earlier than the median survival time of the group. The 'National Radiobiology Archives' project is a comprehensive effort to gather, organize, and catalog data, documents, and tissues related to lifespan radiobiology studies for future research and analyses. The scope of the information system has been expanded to include dose-effect information on approximately 7,000 beagles and 10,000 mice from seven laboratories. An introduction to the system is available on diskette. Dose-effect-relationship studies on inhaled 239pUO2in rats are in progress to obtain lung tumor incidence data at lifetime lung doses of 0.05 to 55 Gy. The incidence of lung tumors was 0.32% in 1877 rats receiving <1 Gy to the lung, 42% in 229 rats receiving >1 Gy, and 0.19% in 1052 controls. Although 1% of deposited plutonium was found in subepithelial locations of upper airways, the dose calculated to upper-airway epithelium from subepithelially located particles was small, and no tumors were observed in the bronchi, trachea, or larynx. No significant difference in tumor frequency, location, or type was found between control and exposed rats, other than for tumors in the lung. Rats exposed by inhalation to radon, radon progeny, and uranium ore dust are being evaluated to determine the influence of dose, dose rate, and cigarette smoke in lung cancer incidence. The overall trend in lung tumor incidence decreases in proportion to th...