Rm LD Research Articles

Linear Discrepancy of Chain Products and Posets with Bounded Degree

The linear discrepancy of a poset P, denoted ld(P), is the minimum, over all linear extensions L, of the maximum distance in L between two elements incomparable in P. With r denoting the maximum vertex degree in the incomparability graph of P, we prove that ${\rm ld}(P)\le \left\lfloor (3r-1)/2 \right\rfloor$ when P has width 2. Tanenbaum, Trenk, and Fishburn asked whether this upper bound holds for all posets. We give a negative answer using a randomized construction of bipartite posets whose linear discrepancy is asymptotic to the trivial upper bound 2r − 1. For products of chains, we give alternative proofs of results obtained independently elsewhere.

The Influence of Butylated Hydroxytoluene-Induced Cell Proliferation on Mouse Lung Damage after X Rays or Fission Neutrons

To examine the relative importance of endothelial cells vs type II alveolar cells in the development of lung damage, we irradiated the lungs of mice with X rays either 2 or 6 days after treatment with butylated hydroxytoluene (BHT) and determined ${\rm LD}_{50/180}$ values. ${\rm LD}_{50/180}$ was 959 rad when no BHT was given, 269 rad when 2 days elapsed after BHT treatment, and 1445 rad at 6 days after BHT. The pattern of response was similar after fission neutron irradiation to the thorax. ${\rm LD}_{50/180}$ after fission neutrons alone was 476 rad, but at 2 and 6 days after BHT, the ${\rm LD}_{50/180}$ values were 98 and 575 rad, respectively. Clearly 2 days after BHT, when radiation injury to type II cells predominated, the sensitivity to both X rays and fission neutrons increased markedly, suggesting that injury to alveolar epithelial cells may be of primary importance in the development of lung damage in the mouse....

Radiation Effects on Membranes: I. Vitamin E Deficiency and Lipid Peroxidation

Mice which had received a vitamin E-deficient diet from weaning on, were more sensitive to X irradiation than were normal mice, ${\rm LD}_{50/30}$ being decreased by 0.25 Gy. The vitamin E-deficient mice also showed an increased spleen shrinkage. The cellular membranes of the vitamin E-deficient mice were more vulnerable to lipid peroxidation. X irradiation in vivo shortened the lag period prior to rapid lipid peroxidation as measured in vitro. Injection of the mice with glutathione prior to X irradiation protected the membranes in the in vitro test of peroxidation capacity as was demonstrated by an extended lag period. The possible meaning of these results with respect to the concept that membranes may be important sites for radiation damage is discussed.

Evaluation of a Nuclease-Resistant Derivative of Poly(I)·Poly(C) [Poly(ICLC)] as a Radioprotective Agent

Intramuscular injection of a stabilized polyriboinosinic acid·polyribocytidylic acid complex, composed of the two acids poly-l-lysine and carboxymethylcellulose [poly(ICLC)], was radioprotective in mice when given in single or multiple doses before total-body irradiation. At low to moderately high dosages, ${\rm LD}_{50/30}$ values were increased significantly (P < 0.05), with a maximum dose-reduction factor of 1.25. Survival rates and weighted mean survival times were also significantly increased. Increased circulating levels of serum interferon proportional to poly(ICLC) concentration were not required at the time of irradiation for radioprotection. Poly(ICLC) was found to have a slight stimulatory effect on the numbers of peripheral blood elements in irradiated mice.

Survival of Drosophila melanogaster Pupa Exposed to Ultrasound

Drosophila melanogaster pupa were exposed to 1-MHz continuous wave ultrasound. Exposure ranged from 0.2 to $4.0 {\rm W}/{\rm cm}^{2}$ (spatially average acoustic intensities) for 10-min continuous exposure. The ${\rm LD}_{50/7}$ was calculated to be $0.7 {\rm W}/{\rm cm}^{2}$. All pupa receiving an exposure greater than $1.5 {\rm W}/{\rm cm}^{2}$ failed to emerge into adults, but a number of these continued to develop to a point 78 hr postexposure. These pupae displayed abnormal eye pigmentation and abnormal eye and thorax development.

Acute Lethality after Fast-Neutron and X-Irradiation of Tribolium confusum

The acute lethal effects of fast neutrons and of X-rays on adults and larvae of T. confusum are compared. The time course of mortality of adults of the Oklahoma strain was the same after midlethal doses of neutrons and X-rays, although the neutrons were about twice as effective as X-rays in producing lethality, based on ${\rm LD}_{50(35)}$. The neutron RBE for adults of the Ebony mutant strain was also about 2, but that for Oklahoma larvae was about 3.85. Larvae surviving midlethal doses of neutrons showed a tendency toward wing abnormalities and delayed pupation. Dose-fractionation recovery with neutron doses in the midlethal range was not detectable in the adults or in the larvae. A considerable sparing effect of dose fractionation was found in X-irradiated adults. Also presented are techniques for using a beam port of a Triga research reactor for fast-neutron irradiation and a method of neutron and gamma dosimetry.

Rapid Screening of Radioprotective Drugs in Vivo

The traditional test for radioprotection, a measurement of the ${\rm LD}_{50/30}$ , requires a 1-mo wait between treatment and result. An alternative method is proposed which requires only a 3-day wait. It requires fewer mice but more man-hours than ${\rm LD}_{50/30}$ measurement. The frequency of micronuclei which result from chromosomal aberrations is the criterion of damage. It is shown that a thiophosphate compound S-2-(3-aminopropylamino) ethylphosphorothioic acid (WR 2721) produced a similar protection measured in this way as had been found by the traditional method.

Radiosensitivity of the Arenicolous Lizard, Uma notata

The radiobiological sensitivity of the arenicolous lizard, Uma notata, was studied. A therapy X-ray unit, operated at maximum output was employed as the source of radiation. The ${\rm LD}_{50(30)}$ and ${\rm LD}_{50(60)}$ were determined and the hematopoietic response after an ${\rm LD}_{50(30)}$ exposure was investigated. The ${\rm LD}_{50(30)}$ exposure for Uma was calculated to be 24,000 R, and the mean survival time was 28 days. The ${\rm LD}_{50(60)}$ was calculated to be 3000 R and the mean survival time 58 days. During the 30-day experimental period after exposure, a significant decrease (95% confidence limits) was observed in spleen weight and granulocyte number. Hematocrits remained within control levels.

Epidermal Changes Produced by Whole Animal Exposure with Low-Energy Accelerated Helium Ions

Some effects of low-energy accelerated helium ion irradiation of essentially the whole skin surface of the mouse (penetration depth $51 {\rm mg}/{\rm cm}^{2}$ ) have been investigated, using doses ranging from 75 to 2800 rads delivered in a single exposure. At this penetration depth, dose-response relationships were obtained for moist desquamation and mortality. For the moist desquamation reaction, 50% of the mouse surface area was involved at a dose of 2918 rads and extrapolation of the moist reaction curve to zero percent skin involvement yields a threshold dose of 1132 rads. Mortality of mice was found with helium-ion doses of 1600 rads or more with an ${\rm LD}_{50(60)}$ value of 2660 rads. This ${\rm LD}_{50(60)}$ value corresponds to involvement of about 43% of the mouse surface in a moist reaction. Mortality occurred between 22 and 42 days postirradiation. The mean survival time of the mice varied between 28.5 and 32.0 days. No dependen...

Effect of Age on the Acute Lethal Response of the Beagle to Cobalt-60 Gamma Radiation

Mortality to 60 days following exposure to60 Co γ-radiation (bilateral, whole-body; 10 min exposure time) has been studied in 387 male and 273 female purebred beagles exposed at various ages from the late fetal stage to adulthood. ${\rm LD}_{50/60}$ values in males and females respectively were estimated to be: 55 day fetus, 324 and 295 R; 2 days post partum, 385 and 408 R; 15 days, 378 and 355 R; 35 days, 322 and 278 R; 63 days, 287 and 270 R; 70 days, 290 and 272 R; and in 1.5-2 yr-old males and 4-6 yr-old females respectively, 316 and 278 R (midline, in-air exposure). Except in animals irradiated prenatally, most deaths occurred 15-20 days post exposure. Bone marrow damage appeared to predominate.

The Effects of Oxygen on Intestinal Crypt Survival in Cobalt-60-Irradiated Mice

Intestinal crypt survival was studied in mice irradiated in air, 100% normobaric oxygen, 100% hyperbaric oxygen (30 psi), and 6% normobaric oxygen. Exposures from 900-2000 R at the rate of 47 R/min. Intestinal crypt survival was determined by the method of Hagemann, Sigdestad, and Lesher (4). The results demonstrated no difference in crypt survival for mice irradiated in air, normobaric oxygen, or hyperbaric oxygen. The crypt survival of mice was shown to have a D0 from 377 to 380 R and a n from 7.9 to 9.7 for mice irradiated in air, 100% oxygen, or 100% oxygen at 30 psi, while mice irradiated in 6% oxygen had a $D_{0}=529$ R with a n=8.1. The DMF (ratio of D0 in 6% oxygen to D0 in oxygen) was found to equal 1.4. The lack of difference in air and oxygen suggests the highly vascularized (oxygenated) gut is maximally sensitive. Animal lethality ( ${\rm LD}_{50(5)}$ ) is compared with crypt survival.

Radioprotective Effect of Rauscher Leukemia Virus in the SJL/J Mouse. II. Development of Radioresistance and the Distribution of Mortality

Studies have been performed to evaluate the development of radioresistance in mice after Rauscher leukemia virus (RLV) infection. In terms of the ability of infected mice to survive the initial 30-day period after exposure to 875 R (a ${\rm LD}_{95/30}$ exposure for normal mice), increased survival became manifested between 6 and 10 days after RLV inoculation. When RLV-injected mice were x-irradiated at 10, 14, 18, 22, 26 and 30 days after infection, the respective 30-day survival values were 47, 47, 20, 52, 33 and 16%. Median survival times were more than doubled in mice irradiated 10 days after RLV infection, and remained elevated. Likewise, an apparent therapeutic effect of radiation on Rauscher disease lethality became manifested on the tenth day of infection and persisted thereafter. However, since posttreatment mortality is the result of two components, radiation-induced mortality and mortality due to Rauscher disease, the 30-day postirradiation survival parameter does not adequately describe the de...

Intestinal Crypt Survival: The Effect of Cobalt-60, 250 kVcp X-Rays and Fission Neutrons

Intestinal crypt survival was studied using the method of Hagemann, Sigdestad and Lesher (8) in mice irradiated with 250 kVcp x-rays, cobalt-60 and fission neutrons. The D0's for the three treatment modalities were 377, 375 and 103 rads with extrapolation numbers of 6.2, 9.2 and 3.1, respectively. The RBE (ratio of D0's relative to x-rays) was 3.6 and 1.0 for neutrons and cobalt-60, respectively. The ${\rm LD}_{50(5)}$ values were found to be 1081 (945-1247), 1365 (1279-1456) and 252 (234-273) rads. The RBE [ratio of ${\rm LD}_{50(5)}$ relative to x-rays] values were found to be 4.3 and 0.8 for neutrons and cobalt-60 irradiation. Intestinal crypt survival varied from 25 to 34% of control at all of the ${\rm LD}_{50(5)}$ values. Total and per crypt cellularity was determined at 3 days postirradiation for each modality. The maximum proliferative response, measured at this time, occurred at or near the ${\rm LD}_{50(5)}$ dose...

The Effect of Exposure Rate on Animal Lethality and Spleen Colony Cell Survival

In this study we examined the response of mice to x-rays delivered at various exposure rates from 2.86 to 105 R/min. Mouse lethality was observed over a 30-day period postirradiation. The ${\rm LD}_{50/30}$ increased with decreasing exposure rate throughout the range studied with the greatest change occurring at lower exposure rates. Survival times and death distributions of the mice were analyzed and the results indicated that the time at which the mice died was independent of the exposure rate employed. The greatest mortality occurred between 9 and 30 days postexposure. From these results, bone marrow injury was interpreted as the primary cause of death of the mice at all exposure rates. The effect of exposure rate variation upon hematopoietic stem cell survival as estimated by the ability to form colonies (CFU) was studied. Cells obtained from the femoral marrows of mice were transplanted into irradiated recipient mice and subsequently irradiated within the recipients. The survival...

Radiation Mortality in the Chinese Hamster, Cricetulus griseus, in Relation to Age

Chinese hamsters (Cricetulus griseus) were given whole-body x-radiation at 1, 3, 7, 15, 30, 71, 100, 150, and 250 days of age. Probit dose-mortality curves, ${\rm LD}_{50(30)}$ values, and mean survival times were determined for each age. The ${\rm LD}_{50(30)}$ values were lowest at 1 day of age (635 rads), increased rapidly to a peak of 983 rads at 100 days of age, and then decreased slightly to 910 rads at 150 and 250 days of age. The age sensitivity of the Chinese hamster was found to be similar to that of the rat but different from the age-sensitivity response of the mouse or dog.

Effect of Circadian Rhythm on the Radiation Response of the Chinese Hamster (Cricetulus griseus)

More than 1000 Chinese hamsters, 80 days old, were used to examine the radiation response of Cricetulus griseus at different times during a 24 hour day. The ${\rm LD}_{50/30}$ values were calculated to be 954 rads (1 AM), 889 rads (9 AM), 823 rads (11 AM), 886 rads (1 PM), and 882 rads (3 PM). Three studies were made to attempt to explain the differences in radiosensitivity: (1) examination of the mitotic indices of white blood cells (WBC) in the bone marrow which showed that the rate of mitosis fluctuated markedly over a 24 hour period, the highest (11 AM) and lowest (1 AM) mitotic index corresponding to the lowest and highest ${\rm LD}_{50/30}$ value, respectively, revealing a linear correlation between ${\rm LD}_{50/30}$ values and rates of mitosis; (2) analysis of the peripheral blood of hamsters irradiated at a time when the mitotic index of WBC was either low or high which showed that the restoration performance of the circulating WBC de...

Mechanisms of Radioprotection of Mice by Phenylhydrazine

Phenylhydrazine is a radioprotector when injected into mice 6 to 11 days before exposure to x-rays. To better define the basis for radioprotection, the following studies were made: effects of phenylhydrazine on ${\rm LD}_{50(30)}$ , hemopoietic regeneration in irradiated mice, hemopoiesis of unirradiated mice, hemopoietic cell radiosensitivity, and life-span of protected mice. Injection of 3.0 mg of the drug a week before irradiation increased the ${\rm LD}_{50(30)}$ by 140 R, which is equivalent to a dose reduction factor of about 1.2. Phenylhydrazine-treated mice survive because of hematologic recovery that becomes manifest 2 weeks after irradiation. Some of the results are consistent with the hypothesis that radioprotection by phenylhydrazine is the result of increased numbers of hemopoietic stem cells in the spleen at the time of irradiation. However, some of the colony-forming unit and splenectomy data indicate that this increase may not be the sole basis for ...

Mortality Response of Mice after Whole-Body Exposure to 1.7-5 MeV Neutrons and X-Rays

The mortality response of male NMRI mice to whole-body irradiation with fast neutrons of the energy range from 1.7 to 5 MeV was studied and compared with the effects of 250 kV x-rays. Fast neutrons were confirmed to be very effective for the induction of early death. With increasing doses of neutrons survival time decreased more rapidly than with x-irradiation so that, in progressing from midlethal to lethal exposures, mean survival time became markedly lower than after equivalent doses of x-rays. The variance in death time was significantly greater in neutron than in x-ray experiments. This reflects the efficiency of additional killing mechanisms attributed to acute gastrointestinal damage. Mean lethal dose was used to determine the relative biological effectiveness of neutrons. The ${\rm LD}_{50(30)}$ was 293 rads for neutrons and 479 rads for x-rays. From these data, taking account of the additional gamma-ray component, the RBE of neutrons was calculated to be 1.5.

Effects of Ionizing Radiation on Survival, Longevity, and Reproduction in Free-Ranging Pocket Mice, Perognathus parvus

There was no significant difference between the responses of captive and free-ranging Great Basin pocket mice, Perognathus parvus, to ionizing radiation. The ${\rm LD}_{50(30)}\pm {\rm SD}$ values were 858 ± 27 rad and 834 ± 32 rad, respectively, and the slopes of both survival curves were parallel. Although some unconfined mice lived 3 years postirradiation, the median longevity was 12 months or less for all dose levels. Median longevity appeared to be inversely related to absorbed dose above the threshold exposure: 675 rad. Radiation-induced sterility was not evident in free-ranging males, but all irradiated females appeared to be permanently sterile in subsequent breeding seasons. Pocket mice were able to survive secondary effects including: swelling and eversion of cheek pockets; depilation; and a change in coat color from tan to white.

Mortality of Mallards Exposed to Gamma Radiation

An ${\rm LD}_{50(30)}$ level of 704 R was calculated for 4-month-old captive mallards. Fifty-five percent of all deaths occurred within the first 16 hours postirradiation. All deaths occurred within 18 days postirradiation. Comparison was made in the rate of dying and the number of deaths between two groups of young game-farm and old wild-caught mallards both given equal high doses of radiation. The percentage of deaths was similar in both groups, but the younger mallards died at a slightly faster rate.