A. C. Upton

Some late effects in mice of ionizing radiation from an experimental nuclear detonation.

The first experimental investigation of the late effects of ionizing radiations from a nuclear detonation in a very large population of mammals (mice) was planned with great care by a team of investigators of the Atomic Energy Commission and the Armed Forces. The animals were placed at various distances from the hypocenter, and the intensity of exposure was monitored by both physical and biological methods. The mice were of the genetically uniform LAF1 strain, of both sexes, and six to twelve weeks of age when exposed. After the early mortality rates had been recorded, the animals were transported to Oak Ridge, where they remained individually caged, the cages randomized in one large animal room, until natural death. Sick animals were killed in extremis. The radiations from the nuclear detonation were composed predominantly of high-energy gamma rays, with a small component of fast and a still smaller component of slow neutrons, the gammaneutron ratios increasing with the distance from ground zero. The par...

INFLUENCE OF AGE AT TIME OF IRRADIATION ON INDUCTION OF LEUKEMIA AND OVARIAN TUMORS IN RF MICE

Summary RF mice exposed to 100-300 r of whole-body X-rays at various ages from before birth to 180 days after birth showed age-dependent variations in susceptibility to leukemia induction. Susceptibility to induction of granulocytic leukemia was minimal when irradiation was carried out during gestation or shortly after birth, rising later to a maximum at about 70 days of age. Susceptibility to induction of thymic lymphomas was, likewise, apparently minimal during gestation but maximal shortly after birth, declining later in life at the time of thymic involution. Susceptibility to induction of ovarian tumors was relatively low in mice irradiated in utero. We are grateful to F. F. Wolff, E. S. Ledford, and W. D. Gude for technical assistance and to Dr. A. W. Kimball for statistical analysis of data.

The Relative Biological Effectiveness of Neutrons, X-Rays, and Gamma Rays for the Production of Lens Opacities: Observations on Mice, Rats, Guinea-Pigs, and Rabbits

The relatively high radiosensitivity of the lens of the eye to neutron radiation is now well established (Evans, 1948; Ham, 1953). In addition to experimental cataracts obtained in several species of neutron-irradiated laboratory animals, lens opacities have been observed in human beings exposed to cyclotron neutrons (Abelson and Kruger, 1949; Dollfus, 1950; Krause and Bond, 1951) and to fission neutrons from atomic detonations (Cogan et al., 1949; Sinskey, 1955). The growing prevalence in our environment of neutron sources such as high-voltage generators (cyclotrons) and reactors makes it increasingly important to know how much neutron radiation the human lens can tolerate. Furthermore, if neutrons are more effective than electromagnetic waves in causing lens opacities, precise comparison of the cataractogenic effects of these radiations should be made to further the knowledge of their fundamental radiobiologic differences. This investigation was undertaken in an attempt to obtain quantitative informatio...

Giemsa staining of autoradiograms prepared with stripping film.

A method is described in which sections or smears of animal tissue are covered with stripping film, exposed and developed for autoradiograms, and stained with modified Giemsa through the film. Results are consistently satisfactory.

ACTH Secreting Transplantable Pituitary Tumors.

Summary and Conclusions Two pituitary tumors occurring in mice exposed to ionizing irradiation proved readily transplantable causing in the recipients obesity with thymic atrophy, hyperglycemia, polyuria, sometimes with glycosuria, severe lymphocytopenia, and hypertrophy of the adrenal cortex. On the basis of these findings it is concluded that this tumor secretes ACTH. There is lack of evidence of stimulation of any endocrine organ other than the adrenal.

A fatal reaction caused by implantation of adult parental spleen tissue in irradiated F1 mice.

Summary 1) Implantation into irradiated F1 hybrids of viable spleen cells from non-irradiated adult mice of the parental strains caused death within 2-4 weeks. 2) The fatal reaction occurred even after sublethal doses of radiation or when the recipients were also injected with marrow cells from isologous hybrids or from mice of the same strain as that from which the parent-strain spleen tissue was obtained. The deaths are ascribed to the formation by the implanted cells of antibodies against the recipient.

Character of agent inducing leukemia in newborn mice.

Summary 1. Tissue extracts from mice of the high-leukemia strain Ak injected into newborn mice greatly increased the leukemia incidence in Rf, DBA 1 and C3Heb mice. and greatly hastened the development of leukemia in AkR mice. 2. Mortality without gross anatomic manifestation of leukemia was also enhanced in extract-injected mice of low-leukemia strains. 3. Although all leukemias in Ak mice were lymphoid with thymic involvement, many leukemias in the low-leukemia strains were of non-thymic types. 4. Transplantation assays of leukemias induced in the low-leukemia strains disclosed a heterogeneity in types, some being related immunogenetically with both host and donor strain. 5. Neither salivary gland nor other tumors were induced by the leukemia agent studied. 6. The available information suggests consideration of a process analogous with DNA-induced transformation (transduction) of genetic properties of microorganisms rather than to a natural type of viral infection.

Radiation-Induced Mouse Leukemia: Consistent Occurrence of an Extra and a Marker Chromosome

Granulocytic leukemia, induced in the primary mouse by x-irradiation, was serially transmitted to RF/Up mice. An extra chromosome, as well as a morphologicaly unusual chromosome, was found in the bone marrow cells of all the leukemic mice that had been injected previously either with leukemic spleen cells or with cell-free ultracentrifugates. This suggests that the changes in the chromosomes are caused by a virus.

GROWTH AND SENESCENCE OF THE BONE MARROW STEM CELL POOL IN RFM/UN MICE.

Summary The exogenous spleen colony assay procedure has been used in RF mice to: (i) measure growth and senescence of the bone marrow stem cell compartment, (ii) compare the radiation sensitivity and recovery capacity of marrow stem cell compartments in fetal vs young adult mice, and (iii) determine residual radiation injury to tissues giving rise to hemopoietic progenitor cells in mice irradiated during fetal development or as young adults. The bone marrow of normal RF mice reached maximum hemopoiesis potential (20.9 CFU/105 nucleated marrow cells) within the first 3 weeks of postnatal life. This value was maintained through the first half of the mouse life. Thereafter, a progressive decline of marrow CFU potential was associated with increasing age of the animals. The stem cell pool in fetal mice appears to be less radiation sensitive and more capable of early recovery from radiation injury than that of 10- to 21-week-old young adults. Senescence of bone marrow stem cell function was accentuated in mice exposed to radiation either during fetal development or as young adults.

Late Somatic Effects in Female RF/Un Mice Irradiated with Single Doses of 14-MeV Fast Neutrons

SummaryRF/Un female mice (∼ 1700 animals), 10–11 weeks old, were given a single whole-body irradiation with 14 meV neutrons (either 0, 50, 100, 200 or 400 rads) at a dose-rate of 1–2 rads/min. The mean age at death for 30-day survivors decreased with increasing dose. The incidence of thymic lymphoma and of myeloid leukaemia increased with dose. The incidence of ovarian tumours increased with dose to a maximum at 100 rads. Radiation enhanced the decline in haematocrit with age. Lens opacities developed in all irradiated groups by 3 months after exposure, progressed at a dose-dependent rate, and ultimately attained a level of severity which greatly exceeded any senile changes in the controls. Other common non-neoplastic diseases were not increased in incidence by irradiation, but all occurred earlier in irradiated animals. The results suggest that 14 meV neutrons are more effective than gamma-rays for shortening life and for producing lens opacities but not necessarily for inducing neoplasms, depending on t...