NOTE The report of the Committee without its annexes appears as Official Records of the General Assembly, Sixty-third Session, Supplement No. 46. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. The country names used in this document are, in most cases, those that were in use at the time the data were collected or the text prepared. In other cases, however, the names have been updated, where this was possible and appropriate, to reflect political changes. Scientific Annexes Annex A. Medical radiation exposures Annex B. Exposures of the public and workers from various sources of radiation INTROdUCTION 1. In the course of the research and development for and the application of atomic energy and nuclear technologies, a number of radiation accidents have occurred. Some of these accidents have resulted in significant health effects and occasionally in fatal outcomes. The application of technologies that make use of radiation is increasingly widespread around the world. Millions of people have occupations related to the use of radiation, and hundreds of millions of individuals benefit from these uses. Facilities using intense radiation sources for energy production and for purposes such as radiotherapy, sterilization of products, preservation of foodstuffs and gamma radiography require special care in the design and operation of equipment to avoid radiation injury to workers or to the public. Experience has shown that such technology is generally used safely, but on occasion controls have been circumvented and serious radiation accidents have ensued. 2. Reviews of radiation exposures from accidents have been presented in previous UNSCEAR reports. The last report containing an exclusive chapter on exposures from accidents was the UNSCEAR 1993 Report [U6]. 3. This annex is aimed at providing a sound basis for conclusions regarding the number of significant radiation accidents that have occurred, the corresponding levels of radiation exposures and numbers of deaths and injuries, and the general trends for various practices. Its conclusions are to be seen in the context of the Committee's overall evaluations of the levels and effects of exposure to ionizing radiation. 4. The Committee's evaluations of public, occupational and medical diagnostic exposures are mostly concerned with chronic exposures of …

sources and effects of ionizing radiation

Sources, Effects and Risks of Ionizing Radiation

Publisher Summary This chapter reviews the sequence of cellular and other changes during cancer development in selected sites in experimental animals and in humans. It highlights the similarities and differences among the carcinogenic processes and discusses the evident generalities and working hypotheses derived from the analyses. It also discusses some perspective concerning the possible relationship of carcinogenesis to other types of chronic pathological processes such as some forms of adaptation and evolution. Major emphasis is given to three sites—namely, skin, liver, and breast. Several other sites or types of neoplasms are also discussed in the chapter, including urinary bladder, brain, kidney, uterine cervix, and foreign-body sarcoma. It focuses on the development of cancer with chemicals in experimental animals and in humans. To date, the major evidence for a beneficial role for new cell populations occurring during the preneoplastic phase of carcinogenesis concerns the liver. However, it seems appropriate to explore other systems from this point of view. In other organs or tissues, appropriate physiological or environmental factors should be sought as possible influences on early carcinogen-induced new cell populations. These influences might well constitute naturally occurring “promoting” environments in at least some carcinogenic process.

The sequential analysis of cancer development.

Comparative study of human and rat mammary tumorigenesis.

Tumors of the mammary gland

Pellets containing 5 mg (/sup 3/H) diethylstilbestrol (DES) and 15 mg cholesterol were implanted S.C. in 84-day-old female Sprague-Dawley (S-D) and ACl rats. DES was released from the implanted pellets exponentially, and the release was not significantly different in S-D rats than in ACl rats. No mammary tumors developed in any treated or untreated S-D rats. In contrast, 90% of the DES-treated ACl rats developed mammary adenocarcinomas. A significant increase in the weight of the pituitary was noted in DES-treated ACl rats. The pituitarities of the treated ACl rats were 2 to 7 times as heavy as were controls, and plasma prolactin levels were 10 to 40 times higher than in controls. In contrast, the pituitaries of treated S-D rats did not significantly increase in weight, and plasma prolactin levels were only 3 to 5 times higher than controls. The uteri of treated S-D rats were significantly heavier than those of control rats and contained large amounts of fluid. This effect was not seen in ACl rats. Although the release of DES from the implanted pellet was essentially the same in ACl and S-D rats, three distinctive strain differences in response to DES were noted: mammary adenocarcinomas were found onlymore » in treated ACl rats; pituitary prolactin-cell adenomas and associated elevated plasma prolactins levels were seen only in treated ACl rats; and pyometritis was induced only in treated S-D rats. Mammary adenocarcinomas and prolactin-cell adenoma responses in the treated ACl rats appear to be correlated with the increasing levels of plasma prolactin. This study demonstrates that the prolonged estrogen treatment of ACl and S-D female rats produces distinctly different mammary and pituitary neoplastic responses. This disparity in neoplastic responses appears to be reflected in the difference of degree to which the hypophysical prolactin cells are stimulated to grow and secrete hormone.« less

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Neoplastic responses and correlated plasma prolactin levels in diethylstilbestrol-treated ACI and Sprague-Dawley rats.

Report of NCI Ad Hoc Working Group on the Risks Associated With Mammography in Mass Screening for the Detection of Breast Cancer

Female noninbred Sprague-Dawley rats were exposed to single doses of 0.28, 0.56, and 0.85 gray (Gy = 1 J/kg or 100 rads) of X-rays or 0.001, 0.004, 0.016, and 0.064 Gy of 430-keV neutrons at 62 +/- 1 days of age and were then observed over the rest of their lives for the appearance of mammary neoplasia. As mammary neoplasms were detected, they were removed and given a classification of adenocarcinoma(s) (AC) or fibroadenoma(s) (FA) after microscopic study. All irradiated groups exhibited an increased incidence of mammary neoplasia. The tumor rate increased steeply with age of the animals, and the effect of the irradiation could be adequately described as a forward shift in time of the spontaneous incidence. The cumulative prevalence was derived from first neoplasms only, and a formalism was presented that makes it possible to derive the integral tumor rate from all neoplasms in all animals. Mortality-corrected cumulative prevalences and integral tumor rates as a function of age were given for the different doses and separately for FA and AC. The mammary FA response and the total mammary neoplastic response (including both FA and AC) were approximately proportional to the absorbed dose of X-rays or the square root of the neutron dose. The relative biological effectiveness (RBE) of the neutrons increased with decreasing dose and reached values exceeding 100 at a neutron dose of 1 mGy; the single dose of 1 mGy of neutrons produced a significant increase of the tumor rate that corresponded to a foward shift or roughly 35 days of the spontaneous incidence. The AC, taken separately, were subject to considerable statistical uncertainties due to their small numbers. However, their RBE-dose dependence was consistent with that for the FA and, even at the highest dose studied, the RBE value exceeded 10. The nonrandom development of multiple FA within individual animals appeared to be the result of differences in susceptibility to radiation. However, mammary FA and AC within individual animals were not statistically correlated.

/pdf/induction-of-mammary-neoplasms-in-the-sprague-dawley-rat-by-5ftqkwvqx2.pdf

Induction of mammary neoplasms in the SPrague-Dawley rat by 430 keV neutrons and X-rays

In a comparative study, female ACI and Sprague-Dawley rats were implanted with pellets containing 5 mg diethylstilbestrol (DES) and 15 mg cholesterol for periods ranging from 2 to 214 days. Strain differences in mammary tumorigenesis, plasma prolactin levels, and gross pituitary responses indicated a desirability for examining the cytology of pituitary glands that were fixed during the course of this study and an immunohistochemical evaluation of their prolactin cell responses. Although plasma prolactin levels were elevated in both strains by 2 days after DES pellet implantation, during the first 10 days of treatment there were no significant increases in pituitary weight in both strains. Pituitary glands from experimental animals of both strains killed on Day 10 exhibited enlarged anti-rat prolactin-binding cells. By Day 28, the pituitary glands of DES-treated ACI rats were significantly enlarged, and a hypertrophic and hyperplastic response of their prolactin cells was detected. From Day 56 to the end of the experiment, gross pituitary tumorigenesis was evident in the ACI but not in the Sprague-Dawley rats. At the microscopic level, adenomatous lesions involving prolactin cell hyperplasia were observed in both strains. Sprague-Dawley and ACI rats exhibited multiple centers of marked vascularization predominated by granular acidophilic cells. These centers were more extensive and larger in the pituitaries of the ACI rats. Two types of immunoreactive prolactin cells were observed in lesioned pituitary glands of both strains: polyhedral, strongly reactive cells which were hypertrophic and more numerous in the ACI rats; and smaller, weakly reactive cells which were numerous in the adenomatous areas of the glands in both strains. It was concluded that the lesions in ACI and Sprague-Dawley females represented different quantitative responses of their prolactin cells to DES treatment.

https://cancerres.aacrjournals.org/content/canres/39/3/779.full.pdf

Influence of diethylstilbestrol treatment on prolactin cells of female ACI and Sprague-Dawley rats

Summary Female Sprague-Dawley rats showed a high incidence of mammary neoplasia and a large number of mammary neoplasms following exposure to a single dose of 500 r of 60Co gamma, total-body radiation. When studied over the entire life-span, these responses were not different when the 500 r were given at either 40 or 160 days of age. Fractionation and protraction of this dose into 4 × 125 r spread over 2 weeks or 8 × 62.5 r spread over 4 weeks or 16 × 31.25 r spread over 8 weeks or 32 × 15.625 r spread over 16 weeks did not change the incidence of rats with mammary neoplasia or the total number of mammary neoplasms compared to a single dose of 500 r. However, a decreased yield of adenofibroma-fibroadenomas and an increased yield of adenocarcinomas were observed. Mammary adenocarcinomas occur very late in the life of nonexposed females long after a significant incidence of adenofibroma-fibroadenomas has been established and then only in a ratio of approximately 1:5. All radiation exposures tended to shift the appearance of the adenocarcinomas forward in time so that they appeared before the adenofibroma-fibroadenomas with the resulting ratio of approximately 1–4 adenocarcinomas to 1 adenofibroma-fibroadenoma.

Claire J. Shellabarger

Papers

Neoplastic responses and correlated plasma prolactin levels in diethylstilbestrol-treated ACI and Sprague-Dawley rats.

Report of NCI Ad Hoc Working Group on the Risks Associated With Mammography in Mass Screening for the Detection of Breast Cancer

Induction of mammary neoplasms in the SPrague-Dawley rat by 430 keV neutrons and X-rays

Influence of diethylstilbestrol treatment on prolactin cells of female ACI and Sprague-Dawley rats

Results of Fractionation and Protraction of Total-Body Radiation on Rat Mammary Neoplasia