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Biomedical subjects

D F Petersen

Publications and source records attributed to D F Petersen.

At least 19 recordsLinked to original sources

Initial comparative response to peak pions and x-rays of normal skin and underlying tissue surrounding superficial metastatic nodules.

Given the limitations of available material and methods for measuring skin response, the relative biological effectivenss (RBE) for the development and healing of skin reaction to pions in this experiment is 1.43. This is based on data obtained from a patient with malignant melanoma, in whom multiple skin nodules and the surrounding normal skin were randomized into three dose levels for pions and x-rays. The RBE for skin reaction was obtained while the skin tumor nodules appeared to regress at least as rapidly with pion therapy as with x-rays. Without benefit of adequate observation of time required for nodule regrowth, any estimate of tumor RBE is speculative.

Dose-Response Relationship, Radiation↗

Biomedical program leading to therapeutic trials on pion radiation at Los Alamos.

Hypoxia and variations in cell cycle phase protect tumor cells being treated with x rays or gamma rays (cobalt). Heavy particles can overcome these protective effects, because of the dense ionization they deposit in tissues. Pions (negative pi mesons) can be directed to and stopped in a specific area, where they are captured by the nuclei of atoms, rendering the nuclei unstable. The nuclei disintegrate, releasing densely ionizing radiation. By confining the dense ionization to the tumor-bearing volume, pions have the potential of increasing the tolerance of the area under treatment to radiation, thus increasing the probability of destroying the tumor. A special channel at the proton factory at the Los Alamos Scientific Laboratory is producing pions for biomedical research. Considerable physical dosimetry has been completed. Cellular studies are underway to provide depth-dose-biological-effect curves. Animal studies will provide information on acute and late effects, which will permit the safe application of pions to a series of anatomical sites established by protocols for radiotherapy clinical trials.

Animals↗

DNA constancy in heteroploidy and the stem line theory of tumors.

Cellular DNA was measured by high-speed flow microfluorometry in mammalian diploid and heteroploid cell populations stained by the fluorescent Feulgen procedure. Heteroploid cells with elevated modal chromosome number showed the expected increase in modal DNA content. However, the variability of DNA content was the same in diploid and heteroploid cell populations despite the large variability of chromosome number in the latter populations. This suggests that heteroploidy may include defects in the chromosomal condensation and kinetochore development systems.

Animals↗

Density invariance of cultured Chinese hamster cells with stage of the mitotic cycle.

Isopycnic banding of Chinese hamster line CHO cells in Ficoll gradients shows that a population in balanced, exponential growth is very homogeneous with respect to density, the coefficient of variation of the density distribution spectrum being less than 5% of the mean reduced density (i.e. density minus one). Similar measurements on synchronized cultures indicate that reduced density varies by less than 2% around the life cycle. The mean density of CHO cells in F-10 growth medium is calculated to be 1.051 after correction for osmotic effects of the Ficoll gradient.

Animals↗

Cell growth and division. IV. Determination of volume growth rate and division probability.

Volume growth rate and division probability functions for mammalian cells have been determined as functions of cell volume with good reproducibility and statistical precision using Coulter volume spectrometry and the equations of the Bell model. Results are compared with independent measurements on synchronous cultures. The slow rate of volume dispersion requires that the growth rate F(tau, V) be closely proportional to volume for cells of a given age. However, when F(tau, V) is averaged over the age distribution of a population in balanced exponential growth to give the growth rate function f(V), the latter may rise more steeply than V.

Animals↗

Radiosensitivity of mammalian cells. 3. Effect of suboptimal growth temperatures on recovery from radiation-induced division delay.

We investigated the effect of suboptimal growth temperatures on recovery from radiation-induced division delay in Chinese hamster cells. It was found that no recovery occurred during the time that either log-phase or synchronized populations were incubated at 4 degrees C and that injury sustained at low dose rates was cumulative over a period of 6.2 hr at low temperature. Postirradiation conditions influencing recovery from the induced division delay period are different from those affecting survival, suggesting that biochemical damage leading to division delay may be different from that leading to cell death.

Animals↗

Radiosensivity of mammalian cells. I. Timing and dose-dependence of radiation-induced division delay.

The time of onset and duration of division delay induced by exposure to 250-kvp x-irradiation have been measured in several mammalian cell lines grown in suspension culture. Unique times of action (i.e. interval from irradiation to cessation of division) late in G(2) are characteristic for HeLa, L-5178Y, and Chinese hamster cells, and the time of action is independent of dose over the range 25-800 rads. The duration of delay was directly proportional to dose; all irradiated cells divided at least once and maintained their relative positions in the life cycle for periods exceeding one generation time. Neither random nor synchronous cultures exposed at varying times in the life cycle exhibited differences in radiation sensitivity measured either by onset or duration of the delay period. The time of action was experimentally indistinguishable from the point marking completion of protein synthesis essential for division, leading to speculation that division delay involves a translation defect.

Animals↗

Radiosensitivity of mammalian cells. II. Radiation effects on macromolecular synthesis.

Radiation effects on macromolecular synthesis essential for the Chinese hamster cell to traverse the life cycle and to divide have been investigated. Life-cycle analysis techniques employing inhibitors of macromolecular synthesis were used in determining the kinetics of cell growth for specific segments of the population following spontaneous recovery from radiation-induced division delay. The results indicated that recovery does not occur in the absence of functional protein synthesis. Under conditions which inhibit normal RNA and DNA synthesis, irradiated cells can recover the capacity to traverse the life cycle and to divide. The stability of mRNA species coding for proteins essential for division in irradiated cells was also measured. The mean functional lifetime of these mRNA species was 1 hr. The data demonstrate the existence of a specific segment of the population consisting of cells which have completed transcription related to division but not concomitant translation and which can recover from the radiation injury without synthesis of additional RNA. Thus, initial recovery of the ability to divide has an obligate requirement for protein synthesis but no corresponding requirement for nucleic acid synthesis during the period when original messenger remains intact.

Animals↗