Action levels for airborne uranium in the workplace: chemical and radiological assessments.

A method is described for deriving two levels of action-an investigation level (IL) and an immediate action level (IAL)-for different forms and mixtures of the natural uranium (U) isotopes 234U, 235U, and 238U in air in the workplace. An IL indicates the need to confirm the validity of moderately elevated measurements of airborne U and adequacy of confinement controls and determine whether work limitations are appropriate. An IAL indicates that safeguards should be put into place immediately, including removal of workers from further exposure until conditions are acceptable. Derivations of ILs and IALs are based on latest radiation protection guidance, information on chemical toxicity of U, and biokinetic models for U. An action level (IL or IAL) is the more restrictive of two derived values, the action level based on U as a chemical hazard and the action level based on U as a radiation hazard.

Complete decay of radionuclides: implications for low-level waste disposal in municipal landfills.

The time required for the complete decay of a radioactive source can be quantified by specifying an acceptable probability and using an original derivation. The physical phenomenon of complete decay may be used as the technical basis to change regulations and permit, with public acceptance, the inexpensive disposal of short half-lived radioactive waste into municipal landfills. Current regulations require isolation of trash from the biosphere for 30 years during the post-closure control period for municipal landfills. Thirty years is sufficient time for complete decay of significant quantities of short-lived radionuclides, and there is a large decay capacity in the nation's landfills. As the major generators of low-level radioactive waste with relatively short half-lives, the academic, medical, and research communities likely would benefit most from such regulatory relief. Disposal of such waste is prohibited or costly. The waste must be specially packaged, stored, transported, and disposed in designated repositories. Regulatory relief can be initiated by citizens since the Administrative Procedures Act gives citizens the right to petition for regulatory change.

Criteria for the administration of KI for thyroid blocking of radioiodine.

Scientific data are reviewed to evaluate the risks of radioiodine uptake and to compare those risks with the benefits and risks of low milligram doses of stable potassium iodide (KI). The limit of 25 rad to the thyroid due to radioiodine uptake is adopted as the "break-even" point above which 130-mg KI doses should be administered. The biological and radiological kinetics of radioiodine for protracted uptakes were derived from the Medical Internal Radiation Dose Committee (MIRD) model (MIRD75). Resulting calculations yielded estimates of dose commitment rates to the thyroid as a function of thyroidal uptake. The extrapolated value of the 1-hr inhalation curve for 131I with 30% uptake compares well with the established MPCa value and intercepts the origin. The calculated KI-blocking efficiency as a function of time after radioiodine uptake agrees well with previously reported experimental data. The prevention or "blocking" of 25 rad to the thyroid was the criterion used to define critical values of radioiodine in the thyroid. Critical values are functions of isotope, the duration of uptake and the elapsed time between inhalation and assay of thyroid content. The presence of radioiodine in the thyroid in amounts greater than the critical value indicates that more than 25 rad to the thyroid can be averted, and KI should be administered in the absence of contraindications. Critical average concentrations are implicitly defined by the method of calculation used in the derivation. Critical average concentrations are presented as criteria for KI administration when assays of the radioiodine content of the thyroid are unavailable. Illustrative applications of critical values and critical average concentrations are presented in the Appendix.

Inhibition of cell cycle progression of human pancreatic carcinoma cells in vitro by L-(alpha S, 5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid, Acivicin (NSC 163501).

The inhibition of cell cycle progression of a human pancreatic carcinoma line, MiaPaCa-2, by L-(alpha S, 5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (Acividin), an antimetabolite and glutamine antagonist, was investigated by means of flow cytometry, cell cycle kinetics, and cell enumeration. Flow cytometric criteria for logarithmically growing MiaPaCa-2 cells were established. Logarithmically growing cells exposed to 50 microM Acivicin appeared to markedly reduce their rate of cell cycle progression after they passed a point in later G1 phase or in early S phase. MiaPaCa-2 cells grew in the presence of 50 microM Acivicin with a population-doubling time of approximately 74 hr compared to a 20-hr doubling time for controls. The inhibition of cell cycle progression was at least partially reversed by removal of the drug. Based on previous reports of the biochemical mechanisms of Acivicin actions, several additives to the tissue culture medium were tested for their ability to protect MiaPaCa-2 cells from inhibition of cell cycle progression. Those cultures which contained cytidine partially protected the cells from Acivicin. The mechanism of inhibited growth induced by exposure to Acivicin is likely a complex reaction to the inhibition of several enzyme systems.

Establishment and cell cycle kinetics of a human squamous cell carcinoma in nude mice and in vitro.

A human squamous cell carcinoma of the virus was xenografted to athymic, nude mice. A tissue culture cell line designated SqCaVu-1H was derived from a second-passage xenograft. The growth characteristics and cell cycle kinetics in the xenografts and in SqCaVu-1H cells were compared. Approximately 80% of the tumor implants produced growing xenografts which had a 2-week latent period followed by Gompertzian growth with a doubling time of 5 to 30 days at 35 days postimplantation. The cell cycle kinetics of the xenografts revealed a heterogeneity from region to region within the tumor. G2 phase and S phase in the xenografts are approximately 8 and 13 hr, respectively. The SqCaVu-1H cells contain only human chromosomes. The modal chromosome number was 64. SqCaVu-1H cells produce plasminogen activator during logarithmic growth, and they produce tumors when injected s.c. into athymic, nude mice. Logarithmically growing SqCaVu-1H cells have a population-doubling time of 21.8 hr in tissue culture. In vitro, their cell cycle duration is approximately 16.0 hr, with G2 phase at 5.6 hr and S phase at 8.6 hr. Comparison of the growth of the same human tumor cells under in vivo and in vitro conditions serves to emphasize that tumor cell proliferation depends strongly on the microenvironment. The varied proliferation characteristics are correlated with their varied inhibition of deoxyuridine incorporation into DNA because of exposure to methotrexate. Logarithmically growing SqVaCu-1H cells had a 50% inhibitory dose of 2.2 X 10(-6) M. Plateau-phase cells in vitro had a 50% inhibitory dose of 9 X 10(-6) M, while the inhibition of cells from the xenografts was nearly dose independent.

Collodion membrane secures cells sorted by flow cytofluorometry onto microscope slides.

Quantitative microscopic cytology of cells previously sorted by flow cytofluorometry has been hindered by the loss of cells from the microscope slide during staining procedures. The simple application of a semi-permeable membrane of collodion over fixed or unfixed cells sorted directly onto a microscope slide secured virtually 100% of the cells onto the slide. Cells covered with the collodion membrane studied with Papanicolaou's stain as well as routine clinical cervical cytologic preparations. In contrast, fewer than one half of the cells sorted onto uncoated or albumin coated slides were retained after staining.

Predominance of granulocytopoiesis in bone marrow grafts in the omenta of mice treated with erythropoietin.

The effects of erythropoietin on the differentiation of murine bone marrow injected into the omenta of x-irradiated mice were investigated. Experimental hosts were injected with 2.5 units of erythropoietin on days 0-7 and sacrificed on day 10. Control hosts were injected with saline or sheep serum. After 10 days the grafts were greater than 95% granulocytic regardless of host treatment. Since these grafts contain multipotent hematopoietic stem cells and the experimental hosts were exposed to large doses of erythropoietin, the results of this experiment indicate that a specialized microenvironment is required for murine erythropoiesis in vivo.

Interkingdom fusion between human (HeLa) cells and tobacco hybrid (GGLL) protoplasts.

The fusion of human HeLa cells with tobacco protoplasts has been accomplished with the use of polyethylene glycol. The sequence from heterocellular adherence to heterokaryon formation has been followed with light microscopy and confirmed by autoradiographs of heterokaryons containing unlabeled tobacco nuclei and tritium-labeled HeLa nuclei. The HeLa nucleus retained its integrity in the tobacco cytoplasm up to 6 days after fusion.

Growth of HeLa cells in diffusion chamber cultures in vivo.

In order to investigate some characteristics of Millipore diffusion chamber cultures (DCC) and their potential for the quantitation of tumor cell growth kinetics, HeLa S-3-cells were grown in diffusion chambers implanted i.p. in mice. HeLa cells grew pseudologarithmically in DCC with a population-doubling time of approximately 2.8 days when 9.2 to 12.0 X 10(5) cells were placed in the chambers initially. The population-doubling time varied as a function of the initial innocula size but was always longer than the in vitro population-doubling time of 1.2 days. Comparable harvests of cells from experiment to experiment varied quantitatively by no more than a factor 1.8. This variaton somewhat limits the use of DCC for the quantitation of subtle effects. The fate and morphology of HeLa cells in DCC were determined from scanning electron microscopy. DCC might be exploited in clinical studies of the growth of patients' tumors and the effects of various therapies in a host-mediated system.