Ethical issues in radiation protection--the 1992 Sievert Lecture.
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Biomedical subjects
Publications and source records attributed to G Silini.
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The main object of this study is to investigate the role of age on the susceptibility to radiation carcinogenesis and life shortening for different qualities of radiation. Over the last few years, a line of research at the Laboratory of Pathology, C.R.E. Casaccia, has been set up to study the effects of exposure to neutron irradiation, including observations on late effects (both neoplastic and nonneoplastic) as a function of radiation dose and of age at irradiation. Graded single doses of X rays or attenuated fission neutrons have been given to male BC3F1 mice 3 and 19 months old and to animals in utero at 17 days postcoitum. The analysis of data from over 3000 mice indicates that irradiation at 3 months of age causes life shortening which is associated with the incidence and rate of radiation-induced neoplasms. Prenatal irradiation or irradiation at 19 months of age does not show a clearly measurable life shortening for both X-ray and neutron exposures. However, significantly higher incidence and rate of solid tumors and reticulum cell sarcomas were observed. In general the data confirm the higher biological effectiveness of neutrons compared with X rays. The estimates of neutron relative biological effectiveness for different end points were found to be in the range of 3 to 18 and their variation was closely dose dependent.
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Quantitative cellular assays of the transplantability of 19 spontaneous reticulum cell sarcomas (RCS) of the BC3F1 mouse were carried out by injecting serial dilutions of monodispersed cells into syngeneic hosts through the intravenous, intracranial and subcutaneous routes. A clear relationship was found between the size of the inoculum and the incidence of tumour takes by all routes, but even for inocula of 5 million cells only 13 tumors grew in one or more of the transplanted recipients. The intravenous route of injection was found to be the most effective, both in terms of the absolute number of tumor takes and the number of cells necessary to produce a given level of takes. The survival of the animals injected intravenously was related to the number of cells received in that earlier deaths occurred with the most concentrated cell suspensions. Attempts to transmit the tumor by cell-free extracts injected into newborn or 1-month-old syngeneic hosts failed to substantiate the possible presence of a specific leukemogenic agent.
(C57BL/Cne x C3H/Cne)F1 mice were splenectomized at 3, 9, or 19 months of age (males) or at 4 months of age (females) and observed until spontaneous death. Their mean lifespans were only slightly increased by splenectomy, but the final incidence of and age-specific death rate from reticulum cell sarcoma (RCS) were significantly decreased; the latter effect was associated with prolonged latency times of neoplastic expression. Splenectomized females had a more pronounced decrease in incidence of and rate of death from RCS than did males. Lethally irradiated male mice were inoculated with isogeneic spleen cells from young (3 mo of age) or old (12-18 mo of age) untreated male donors, and the animals surviving acute radiation effects were also observed until spontaneous death. In spite of the fact that the mean life-spans of the spleen-repopulated animals were slightly shortened, age-specific death rate analysis showed that the rate of RCS incidence approached that of untreated controls of comparable ages. The combined results of splenectomy and spleen cell transplantation strongly indicated that some cells in the spleens of these mice have a high probability of being transformed into potentially neoplastic progenitor cells with long latency between cell transformation and overt tumor growth.
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Lethally-irradiated mice received a graft of bone-marrow cells obtained from intact syngeneic animals or from donors pre-irradiated with 200 or 400 rad. The numbers of haemopoietic cells injected were sufficient to give a high percentage of recipients which survived short-term bone-marrow failure. Epidemiological and pathological observations on long-term surviving animals showed an increased incidence of nephrosclerosis and of systemic or solid tumours following different relationships with the radiation dose given to the cells. These data are discussed within the framework of an experimental model system which might allow estimates of incidence of some neoplastic diseases according to cellular hypotheses of tumour induction.
The respective role of the spleen or of the bone marrow in the regeneration of the haemopoietic progenitor compartment of heavily-irradiated mice has been investigated. Splenectomy was used to this end in animals injected with exogenous isogenic cells or regenerating from endogenous spleen or marrow cells. Analysis of the data as a function of time shows that the presence of the spleen affects marrow CFU repopulation only at the early post-irradiation stages. The expansion of the marrow progenitor pool proceeds, however, rather independently of the spleen and marrow CFU remain eventually as the main source of haemopoietic cells in the surviving mice. Thus the reaction of the spleen may be envisaged as a fast, important but transient contribution to the overall haemopoietic function of heavily-irradiated animals.
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