[en] In this review, low-dose levels for high- and low-LET radiation are defined to be <5 cGy and <20 cGy, respectively, and the data of various long-term mouse studies performed at Centro Casaccia's laboratories are considered especially on the analysis of the available results of the dose regions within 17 cGy for neutrons and 32 cGy for X-rays. Particularly, mouse studies are described on treatment with single doses of 1.5 MeV neutrons or 250-kVp X-rays, with fractionated or acute doses of fission neutrons, with in utero single doses of fission neutrons or 250-kVp X-rays and with single doses of fission neutrons in another mouse strain. In all cases the analysis object considered is the animal-at-risk and ovary and solid neoplasms are discussed. Data seem to reinforce the idea that at low doses the effectiveness of ionizing radiation is in practice very low in inducing neoplasms in the laboratory mouse. (K.H.)

[en] Complete observation of survival and late pathology was conducted on over 2000 female mice irradiated with single doses of 1.5 MeV neutrons (5, 10, 20, 40, 80, 160 mGy) and X rays (40, 80, 160, 320, 640, 1280, 2560 mGy). The results showed a statistically life shortening for neutron doses not lower than 80 mGy. Assuming linear non-threshold dose-effect relationships for both radiation qualities, a neutron RBE of 12.3 was obtained. Solid tumour induction was also significant from a neutron dose of 80 mGy and for X-ray doses larger than 1 Gy. No sublinear dependence of the carcinogenic effect on low neutron doses was seen. Separate examination of ovarian tumour induction indicated that a threshold dose is likely to exist, especially for X rays. A trend analysis of the neoplasm incidence confirmed the above findings. Death rate analysis by the Weibull model showed agreement between the shift to earlier times and tumour induction. (author)

[en] The present analysis of data on the induction of lymphoma and myeloid leukemia in BC3F1 mice has indicated some new and interesting aspects regarding the shapes of the dose-effect curves. The incidence data can be interpreted by radiobiological models of the induction process coupled with cell inactivation. In particular, for malignant lymphoma the dose-response curve after X rays can be described assuming a quadratic model corrected for cell inactivation, while the incidence data after fission neutrons are best fitted by a linear model which also allows for cell inactivation. Myeloid leukemia has also been induced in BC3F1 mice. The bell-shaped dose-response curves observed after irradiation with either X rays or neutrons are explained by assuming simultaneous initial transforming events and cell inactivation with the data for cell inactivation at higher doses being in agreement with data reported for other strains of mice. A value for relative biological effectiveness of 4 is obtained at the lowest neutron dose used. The value of the inactivation parameters can be compared with those of the cell inactivation probability per unit dose for the bone marrow hematopoietic stem cells, which are believed to be the target cells for these tumors

[en] The induction of liver tumors has been studied in BC3F1 male mice after acute whole-body irradiation with fission neutrons and X rays, given at different ages. In prenatally irradiated mice, a small effect is seen after doses of 0.3 to 2.1 Gy of X rays, and a more pronounced effect is found after neutron doses of 0.09 to 0.62 Gy. At 3 months of age the animals show a higher incidence after X-ray doses from 2 Gy, and for neutrons from 0.17 Gy. At 19 months of age, liver tumors are rarely induced by either type of radiation. These findings are confirmed by the statistical analysis of trend. The possibility of deriving dose-response relationships for liver tumors was also investigated. In the dose ranges where the risk appears to increase as a function of the increase in dose, the data points for neutrons were well fitted by a linear expression. A pure quadratic relationship best fitted the X-ray data. Using these expressions, the RBE for neutrons was 28 at 0.09 Gy for prenatal irradiation and 13 at 0.17 Gy for irradiation at 3 months. This suggests the existence of a risk of developing liver tumors after exposure to radiation, and fetal liver seems to be particularly sensitive to neoplastic transformation. This risk may be negligible at low doses (less than 1 Gy) of low-LET radiation, or with exposure at older ages

[en] This paper presents a review of several studies conducted in our laboratory to examine the carcinogenic effects in mice of high-LET radiation, and for comparison of low-LET reference radiation. For some specific end-points the following conclusions can be formulated: 1) the dose-response curves for myeloid leukemia and malignant lymphoma can be interpreted in terms of induction and inactivation; in particular, the data confirmed that a linear depenence of the induction on dose is adequate to describe the response to fission neutrons, while a pure quadratic dependence is consistent with the experimental data for low-LET radiation; 2) in the liver, a marked age-dependence was demonstrated for radiation-induced tumors with a much higher susceptability in young than in old mice; also for these tumors the dose-effect curves can be described by a linear and a quadratic relationships for high- and low-LET radiation, respectively; 3) data on ovarian tumor induction suggested threshold-like dose responses; these peculiar shapes as well as the absence of a clear radiation quality dependence of the curves are difficult findings to explain using a simple model of radiation action, and they might better be related to a non-stochastic effect of hormonal imbalance following irradiation. (author)

[en] Experimental studies, when carried out under well controlled experimental conditions and planned to investigate specific endpoints, can provide reliable information on many aspects of the biological action of radiation. In particular, animal studies are suitable to help in determining the shapes of the dose-response relationships for tumour induction, and the influence of dose rate, and in understanding the species and strain dependence, as well as the effect of factors such as sex, age and hormonal status. All these variables can diversely influence the biological response to radiations of different qualities, and thus the RBEs. These aspects are examined and discussed in the paper, special attention being addressed to the tumour induction to response of the haemolymphopoietic tissue and of epithetial tissues, such as liver and ovary, which have shown an appreciable degree of susceptibility to radiation carcinogenesis. (author)

[en] 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. 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. 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

[en] An experimental study of male and female CBA/Cne mice was set up at Casaccia primarily to investigate the influence of sex on long-term survival and tumor induction after exposure to high- and low-LET radiation. Mice were whole-body-irradiated at 3 months of age with fission-neutron doses of 0.1, 0.2, 0.4, 0.8, 1.2 and 1.8 Gy at the RSV-TAPIRO reactor (mean neutron energy 0.4 MeV, in terms of kerma, y_D = 51.5 KeV/μm), or with 250 KVp X-ray doses of 1, 3, 5 and 7 Gy. Control and irradiated animals were then followed for their entire life span. As a general finding, male CBA/Cne mice appear more susceptible to tumori-genesis than females. In particular, the incidences of induced acute myeloid leukemia and malignant lymphomas are significant only in male mice. Benign and malignant solid tumors of many types are observed in mice of both sexes, the most frequent being in the lung, liver and ovary. However, evidence for a radiation response is limited to the case of Harderian gland neoplasms. In addition, a comparison of the observed frequency of all irradiated compared to unirradiated animals bearing solid tumors shows that the total tumor occurrence is not altered markedly by radiation exposure. A decrease in survival time is observed for both sexes and radiation types and correlates well with increasing dose. Moreover, both sex and radiation quality appear to influence the life shortening. A similar dose dependence of survival time is found when tumor-free animals alone are considered, suggesting a non-specific component of life-shortening. 18 refs., 3 figs., 5 tabs

[en] Late somatic effects of total lymphoid irradiation have been investigated in BC3F1 mice. A total X-ray dose of 34 Gy was distributed in 17 daily fractions. The cumulative mortality curve is shifted in time because all the irradiated mice died earlier than the unirradiated controls. There was a 24% shortening of life span. A marked increase of solid tumor incidence, mostly due to skin cancers, was observed (66% vs 30%). In contrast, the incidence of malignant lymphomas was greatly reduced in irradiated mice (6% vs 49%). Furthermore, nephrosclerosis was a common finding in the irradiated group (38% vs 8%). Death-rate analysis revealed an association between life shortening and the presence of solid tumors and nephrosclerosis at death

[en] Extension of previous investigations at this laboratory regarding life shortening and tumor induction in the mouse has provided more complete dose-response information in the low dose region of X rays and neutrons. A complete observation of survival and late pathology has been carried out on over 2000 BC3F1 female mice irradiated with single doses of 1.5 MeV neutrons (0.5, 1, 2, 4, 8, 16 cGy) and, for comparison, of X rays (4, 8, 16, 32, 64, 128, 256 cGy). Data analysis has shown that a significant life shortening is observable only for individual neutron doses not lower than 8 cGy. Nevertheless, assuming a linear nonthreshold form for the overall dose-effect relationships of both radiation qualities, an RBE value of 12.3 is obtained for the 1.5 MeV neutrons. The induction of solid tumors by neutrons becomes statistically significant at individual doses from 8 cGy and by X rays for doses larger than 1 Gy. Linear dependence on neutron dose appears adequate to interpret the data at low doses. A separate analysis of ovarian tumor induction substantiates the hypothesis of a threshold dose for the X rays, while this is not strictly needed to interpret the neutron data. A trend analysis conducted on the neoplasm incidence confirms the above findings. Death rates have been analyzed, and a general agreement between the shift to earlier times of these curves and tumor induction was found