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Biomedical subjects

D K Myers

Publications and source records attributed to D K Myers.

At least 19 recordsLinked to original sources
PubMed1995

Relative biological effectiveness of tritium for induction of myeloid leukemia in CBA/H mice.

To help resolve uncertainties as to the most appropriate weighting factor for tritium beta rays, a large experiment was carried out to measure the relative biological effectiveness (RBE) of tritiated water compared to X rays for the induction of myeloid leukemia in male mice of the CBA/H strain. The study was designed to estimate the lifetime incidence of myeloid leukemia in seven groups of about 750 mice each; radiation exposures were approximately 0, 1, 2 and 3 Gy both for tritiated water and for X rays. The lifetime incidence of leukemia in these mice increased from 0.13% in the control group to 6-8% in groups exposed to higher radiation doses. The results were fitted to various equations relating leukemia incidence to radiation dose, using both the raw data and data corrected for cumulative mouse-days at risk. The calculated RBE values for tritium beta rays compared to X rays ranged from 1.0 +/- 0.5 to 1.3 +/- 0.3. A best estimate of the RBE for this experiment was about 1.2 +/- 0.3. A wR value of 1 would thus appear to be more appropriate than a wR of 2 for tritium beta rays.

Animals↗
PubMed1989

Dose-rate effects of mammary tumor development in female Sprague-Dawley rats exposed to X and gamma radiation.

Mammary tumour development was followed in two experiments involving a total of 2229 female Sprague-Dawley rats exposed to various doses of X or gamma rays at different dose rates. The data for another 462 rats exposed to tritiated water in one of these experiments were also analyzed. The incidence of adenocarcinomas and fibroadenomas at a given time after exposure increased linearly in proportion to total radiation dose for most groups. However, no significant increase in adenocarcinomas was observed with chronic gamma exposures up to 1.1 Gy, and the increase in fibroadenomas observed with chronic gamma exposures at a dose rate of 0.0076 Gy h-1 up to an accumulated dose of 3.3 Gy was small compared to that observed after acute exposures. The incidence of all mammary tumors increased almost linearly with the log of dose rate in the range 0.0076 to 26.3 Gy h-1 for 3 Gy total dose of gamma rays. The effects of X rays appeared to be less influenced by dose rate than were the effects of gamma rays.

Adenocarcinoma↗
PubMed1988

Impact on radiogenic cancer risk of persons exhibiting abnormal sensitivity to ionizing radiation.

Human genotypes are known "that confer both increased susceptibility or resistance to DNA damage and increased cancer risk after exposure to carcinogenic agents, including ionizing radiation" (NAS 1980). The existence of sensitive subgroups at elevated risk, if they are of appreciable size, could have significant impact on the actual distribution of risk. The radiosensitive disorder ataxia-telangiectasia (A-T) serves as a good example: the significant "at risk" group, A-T heterozygotes, is estimated to comprise between 0.5% and 5% of the total population, and has a twofold elevated lifetime risk of fatal neoplasia. Other genetic syndromes that manifest abnormal radiosensitivity are also known, but no estimates are available for the population frequency of all such phenotypes, or for their overall degree of increased risk. As the first part of a program addressing these questions, we have developed a rapid and inexpensive assay for screening members of the general population for abnormal radiosensitivity; such persons would be regarded as at presumptive elevated risk of radiogenic cancer. Our method utilizes lymphoblastoid cell lines and chronic as opposed to acute gamma-ray exposure to amplify the difference between normal and somewhat sensitive strains. A simple "grow-back" assay assesses the survival response. Information on the extent of natural variation in inherited susceptibility to radiogenic cancers could be most useful for radiation protection in the future.

Cell Line↗
PubMed1987

Some factors affecting the sensitivity of cultured human cells to high-LET radiation.

Comparative effects of decay of DNA-bound 125I, of gamma-radiation and of tritiated water on survival of the proliferative ability of cultured cells were examined. The results confirm a previous report that cells frozen to -196 degrees C in the presence of 2M glycerol have lost a considerable proportion of their intracellular water. The data also suggest that the fraction of the lethal damage caused by deposition of radiation energy in intracellular water close to the DNA is greater for gamma-radiation than for the decay of DNA-bound 125I. Inherited differences in the sensitivity of untransformed fibroblasts from individual humans to ionizing radiations and other DNA-damaging agents are being explored. The ratios of the sensitivities of various cell lines to particular agents can vary several-fold. Thus the RBE of various radiations is affected not only by the irradiation conditions and the water content of the cells but also by inherited abnormalities in the DNA repair systems in human cells.

Animals↗
PubMed1984

Occurrence of mammary tumors in rats after exposure to tritium beta rays and 200-kVp X rays.

The RBE for tritium was estimated in reference to 200-kVp X rays, using acceleration of breast tumor appearance in the female Sprague-Dawley rat as the end-point. Chronic X-ray doses of 0.3-2.0 Gy were delivered over 10 days. Intraperitoneal injections of tritiated water ranging in concentrations from 45 to 370 MBq/100 g body wt were administered, followed by four additional injections at 2-day intervals and half of the initial concentrations. Seventy-five percent of the total tritium dose was delivered to the mammary gland within the first 10 days and 95% within the first 20 days after the start of the tritium exposure. RBE estimations were based on various criteria including the tumor incidence per Gy at 450 days postirradiation and the time required to induce tumors in 50% of the animals at risk. The results suggest that tritium beta rays are about 1.1-1.3 times more effective than chronic 200-kVp X rays for acceleration of the appearance of rat mammary tumors. However, the uncertainties involved in these calculations are such that the effects of tritium beta rays could not be reliably distinguished from those of chronic 200-kVp X rays. Measured differences in RBE values were slightly larger for the comparison between acute and chronic X rays than for the comparison between chronic tritium beta rays and chronic X rays.

Animals↗
PubMed1978

Repair of the double-strand breaks produced by 125I disintegrations in the DNA of Micrococcus radiodurans.

Wild-type M. radiodurans and two radiosensitive mutants were used to study the lethal effects of 125I disintegrations in their DNA. The relative sensitivities of these three strains to inactivation by gamma-radiation were reflected in their relative sensitivities to inactivation by 125I decay. The number of double-strand (ds) breaks in the DNA appeared to be similar at levels of gamma-radiation and of 125I decay that reduced survival to 10%. All three strains of M. radiodurans rapidly repaired ds breaks produced in their DNA by either gamma-radiation or 125I disintegrations. If one ds break per is a lethal event [Kirsch et al., 1975], cells of the three strains tested would die only when they had left unrepaired one ds break out of an initial 45,600 or 1800 ds breaks per single cell.

Cell Survival↗
PubMed1976

DNA turnover and thymidine re-utilization in mouse tissues.

Mice were injected intravenously with tritiated thymidine (TdR) and 125I-labeled iododeoxyuridine (IUdR) in low doses to provide a simultaneous labeling of tissue DNA with non-toxic amounts of these two precursors. The total activity per organ and the ratio of the two isotopes was measured in the DNA at various times between 1 and 15 days after the injection. Since TdR from dying cells is re-utilized more effeciently than IUdR from the same cells, more labeled TdR than IUdR was retained in the tissue DNA in these experiments. From the slopes of the regression lines, the true rated of turnover of replicating tissue DNA and the per cent re-utilization of TdR were calculated. Re-utilization of TdR varied from 37 to 60% in the six tissues examined.

Animals↗
PubMed1975

Incorporation of thymidine and iodeoxyuridine in mammalian cells in vitro.

The incorporation of labelled thymidine (dT) and iododeoxyuridine (IdU) into DNA was studied with tissue culture cells and with normal mouse cells in vitro. The rates of incorporation and the ratio dT/IdU incorporation both varied from one type of cell to another and from one suspending medium to another. Despite the known complexity of the regulation of DNA synthesis, the data for incorporation of exogenous dT and IdU could be fitted reasonably well by a model for single-step enzymic process. Deviations from the theoretical predictions were minimal in the presence of fluorodeoxyuridine.

Binding, Competitive↗
PubMed1975

Double labeling with [3H]thymidine and [125I]iododeoxyuridine as a method for determining the fate of injected DNA and cells in vivo.

Mice were injected intravenously and intraperitoneally with preparations of intestinal nucleoprotein, spleen nuclei, mouse thymus cells, or human kidney T cells whose DNA had been labeled with both [3H]thymidine (TdR) and [125I]-iododeoxyuridine (IUdR). Since free TdR is reutilized more efficiently than free IUdR produced by enzymic hydrolysis of the exogenous DNA, the ratio of [3H]TdR/[125I]IUdR in the DNA fraction of the tissues of the recipient mice provides a measure of the amount of intact exogenous DNA in the tissue. In most instances, the doubly labeled exogenous DNA was almost completely hydrolyzed within 1 day injection, but survival of the DNA from whole cells could be demonstrated in some cases.

Animals↗
PubMed1975

Inhibition and amplification of the radiation-induced degradation of DNA in Escherichia coli.

The degradation of DNA in a repair-proficient strain (B/r) and in two repair-defective strains (Bs-1 and pol A) of Escherichia coli was studied in the presence and absence of three metabolic inhibitors after exposure of the cells to X-radiation. The radiation-induced degradation of DNA was dependent on energy production in freshly harvested log-phase cells and was closely related to the repair capacity of the cells. A different system, probably involving nonspecific deoxyribonucleases acting at radiation-induced strand breaks, appeared to be responsible for the degradative processes in stationary-phase cells or in log-phase cells which had been aged by standing in buffered saline for 2 days before irradiation. The three inhibitors tested (caffeine, rifampin, and carbonyl cyanide m-chlorophenyl hydrazone) were all found to inhibit partially the radiation-induced degradation of DNA in E. coli cells. Under other conditions, the same three compounds amplified the degradative process. The data suggested that the amplification was due to a selective inhibition of repair processes. The degradative processes which were stimulated by X-radiation of E. coli cells show many parallels to those which are evoked by phleomycin or colicine.

Caffeine↗
PubMed1975

Incorporation of thymidine and iododeoxyuridine into the DNA of mouse tissues.

Mice were injected intravenously with a solution containing tritiated thymidine (TdR) and iodine-labelled iododeoxyuridine (IUdR). The ratio of 3H/125I activities was measured in the acid-soluble fraction and in the DNA of several tissues at various times from 0.08 to 24 h after injection. There did not appear to be any discrimination in favor of TdR in the acid-soluble fraction of the tissues. The amount of TdR incorporated into the DNA was four to five times greater than the amount of IUdR incorporated; moreover, this value remained relatively constant throughout the period of DNA synthesis under the conditions used. Although IUdR was destroyed more rapidly than TdR in the body, particularly at high concentrations of both precursors, this factor did not account for the major portion of the discrimination observed with tracer amounts of the two DNA precursors. Discrimination in favor of TdR as a precursor for DNA must, therefore, occur at some stage in the utilization of intracellular precursor.

Animals↗