Anna Goldfeder

Relation between Radiation Effects and Cell Viability as Indicated by Induced Resistance to Transplanted Tumors1

In a study of the effects of x-radiation upon the proliferation of implants of mouse sarcoma 180 in vivo, following irradiation in vitro (1), it was shown that with the increase of the x-ray dose up to 2,000 r there occurred a decrease in the percentage of takes and an increase in percentage of regressions among tumors which originated from the irradiated implants. Doses of 2,200 to 3,000 r applied to tumor fragments permitted only small percentages of takes, while doses from 4,000 to 5,000 r entirely prevented the irradiated implants from producing a detectable tumor. Although no detectable tumor growth occurred, however, the inoculated animals became resistant to subsequent non-irradiated tumor implants just as did those animals in which established tumors regressed. In previous experiments (2) it was shown that a dose of 60,000 r was required to prevent the proliferation in vitro of explants of the same type of tumor (sarcoma 180). To throw some light on the observed fact that much larger doses are nec...

Further Studies on the Effects of Irradiation on Proliferation and Metabolic Processes of Normal and Malignant Tissues

THE time-intensity factor related to the effectiveness of irradiation upon living processes remains to-day an unsettled problem among the investigators in this specialized field. The question as to whether high dosage rates for a short time or low dosage rates for a long period of exposure produce more marked effects of radiation has not yet been definitely answered. The present series of experiments was undertaken in an attempt to throw some light upon this question. Before presenting the results obtained from these experiments, reference will be made to our previous investigation (1). The determination of the lethal and sublethal doses produced by different types of radiation for various tissues grown in vitro was chosen as a basis for that investigation. The following technic and criteria were used: Freshly excised tissue fragments embedded in a nutritive medium on a No. 1 coverslip and covered with a mica sheet were inverted over a hollow ground slide, sealed with paraffin wax, and irradiated. The irr...

The Effect of Radiation on Cell Respiration

THE purpose of this experiment was to correlate the effect of various types of radiation on the growth and respiration of mammalian tissues in vitro. The results of the effect of x-rays, radium, and radon upon growth in vitro are recorded in a separate paper. We were able to determine the lethal dose and sublethal dose of these three types of radiation for tissues of various origin grown in vitro. As in the experiments on proliferation, we have also attempted to determine the effective dose of radiation for respiration. Material and Experimental Procedure In a previous communication (1) we reported the values of O2 uptake and the respiratory quotients of normal mouse kidneys which showed the most uniform respiration. This type of tissue was, therefore, selected for the experiment with radiation. The kidneys removed under aseptic precautions from three- to four-month-old mice, immediately after pitting, were placed in hollow ground Maximovs slides, a small strip of moist filter paper was placed beside the...

Further Studies on the Relation Between Radiation Effects, Cell Viability, and Induced Resistance to Malignant Growth

In a previous study (1) attempts were made to correlate the effects of irradiation on living processes observed in experiments carried out in vitro with radiation effects in vivo. Mouse sarcoma 180 was used as an experimental subject in both procedures. While a dose of about 60,000 r in air was required to prevent the growth of tumor particles in a culture medium, a dose of 4,000 to 5,000 r in air applied to similar tumor particles prior to implantation was sufficient to prevent their proliferation in the animal organism. The implanted tumor fragments previously irradiated with dosages in the neighborhood of 5,000 r in air rendered the animals resistant to subsequent viable (non-irradiated) implants of the same type of tumor. In these animals no detectable tumor developed; that is, they became immune to tumor growth. On the other hand, animals implanted with fragments previously irradiated with dosages of about 60,000 r in air failed to show any such resistance. The massive dose (60,000 r in air), therefo...

NEWER ASPECTS IN CELLULAR RADIOSENSITIVITY

Why cells differ in their response to ionizing radiation is a recurrent question among investigators in the field of radiobiology, stressed again in two recent review papers (1, 2). The results herein reported seem to shed light on this query. For a number of years the authors interest has been focused mainly on the unraveling of the factor(s) involved in differential cellular radiosensitivity. This interest evolved from her earliest experiments which demonstrated that when mixed cells of tissues, such as kidneys, tongue, and heart, were exposed in vitro to ionizing radiation (x-rays or radium), the lymphocytes, granulocytes, macrophages, and fibroblasts were gradually destroyed by increased radiation doses, whereas the epithelial cells continued to proliferate (3). Subsequent experiments demonstrated a difference in radiosensitivity between two analogous mammary tumors (4). In the hope of elucidating this phenomenon, experiments were directed toward the detection of intrinsic properties of specific cell...

Further Studies on Effects of Irradiation on Proliferation and Metabolic Processes of Normal and Malignant Mammalian Tissues

Aprevious communication (1) recorded effects produced by different dosage rates of x-radiation on the proliferation in vitro of various mammalian tissues, both normal and malignant. In the present series of experiments the attempt was made to evaluate the time intensity factor for given doses of filtered and unfiltered x-radiation in relation to their effect upon growth factors of mouse sarcoma 180 grown in vivo following irradiation in vitro. Material and Experimental Procedure Tiny fragments of mouse sarcoma 180 were used as test objects. The technic was that employed in the previous experiments (1) except that the tissue fragments were implanted subcutaneously in both axillae of each mouse instead of in a culture medium. Tumors about eight to ten days old were removed from the animals under strict aseptic precautions and cut into tiny fragments with very sharp scissors. Portions of the cut tumor fragments were spread on a round coverslip, No.1 (22 mm. diameter), previously attached to a square mica she...

Further Studies on the Radiosensitivity of the Analogous Mouse Mammary Tumors dbrB and C3H

The purpose of this communication is to present a survey of findings from an extensive series of experiments on the radiobiological characteristics of two analogous mouse mammary tumors. An attempt will be made to interpret several interesting phenomena which were brought to light during the course of this research, and finally, a discussion will be presented of a possible technic for radiation therapy which arises logically from a consideration of these and previous results. The presentation is in three parts which correspond to the three phases which have evolved from this work: For the sake of clarity a concise summary of previous findings and background will first be given. The mammary tumor of the dba strain of mice, designated the dbrB tumor, diagnosed as an adenocarcinoma, has a latent period2 of about four to six days and results in the death of the host within three weeks. The mammary tumor of the C3H strain of mice, referred to as the C3H tumor, and also diagnosed as an adenocarcinoma has a late...

Further Studies on the Radiosensitivity of Tumors Autogenous to Homozygous Hosts

In a previous communication (1), it was demonstrated that two analogous mammary tumors, both histologically diagnosed as adenocarcinoma, differed widely in regard to radiosensitivity. Thus, implants of an adenocarcinoma grown in one inbred strain of mice (C3H) required a dose of about 2,700–2,800 r to prevent proliferation upon reimplantation into hosts of the same inbred strain, while implants of a second mammary tumor, grown in another inbred strain (dba), and designated dbrB, required about 5,000 r. An attempt is being made to throw some light on the question as to why two analogous tumors of the same histologic structure, grown in the strains of mice in which they originated, should differ so markedly in radiosensitivity. With this in view, the growth characteristics of these two tumors in tissue culture, irradiated and non-irradiated, and their metabolic activity in vitro were studied. The observations made in the course of this study will be briefly presented here. Experimental Procedure For the cul...

Relationship Between Morphology and X-Ray Effects in Implants of Mouse Sarcoma 180 Irradiated with 5,000 and 60,000 Roentgens (in Air)

The experiment to be described in this paper deals with the morphology of implants of mouse sarcoma 180 previously irradiated with 5,000 r (in air), as compared with that of implants irradiated with 60,000 r (in air) and unirradiated controls, as they appeared during ten successive days following implantation into 100 per cent susceptible mice. This is an extension of previous investigations in which it was demonstrated (a) that a dose of 60,000 r, measured in air, was required to prevent the proliferation of explants of mouse sarcoma 180 in a culture medium in vitro (1); (b) that a dose of 5,000 r was sufficient to prevent implants from producing a detectable tumor in vivo in a strain in which control implants were 100 per cent successful (2); (c) that animals implanted with tumor fragments irradiated with 5,000 r became resistant to subsequent implants of the same type of tumor, while those animals implanted with tumor fragments irradiated with 60,000 r did not (3). Several authors (4–9) have investigat...