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Biomedical subjects

M Coppola

Publications and source records attributed to M Coppola.

At least 73 records · Page 4Linked to original sources

The dose-response relationships for myeloid leukemia and malignant lymphoma in BC3F1 mice.

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.

Animals↗

Late somatic effects in mice after total lymphoid irradiation.

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.

Animals↗

Surgical management of ileosigmoid fistulas in Crohn's disease.

Radiologic and endoscopic demonstration of ileosigmoid fistulas is difficult: some are discovered only at operation. In these cases the surgeon is faced with the decision of either to remove "en bloc " the involved bowel or to simply close the sigmoid defect. Twelve patients with Crohn's disease complicated by ileosigmoid fistulas were operated: 7 by ileal and/or colonic resection and simple closure of the sigmoid fistula, 4 by double resection and 1 by total colectomy. Stomas were performed in 2. The review of this experience demonstrated that conservative surgery is effective and safe in most cases. Local extended resection should be reserved to cases where secondary involvement of a rather long segment of the intestine is present or where the sigmoid and rectum are primarily involved by active severe Crohn's disease. In these cases, a protective stoma may be considered.

Adolescent↗

Tumor induction and life shortening in BC3F1 female mice at low doses of fast neutrons and X rays.

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.

Animals↗

Relative frequency of acentrics to dicentrics caused by radiation and by chemical action on human lymphocytes.

Various concentrations of sodium iothalamate were added to human blood samples before exposure to X-rays, in order to investigate the dependence of the frequency ratio of acentrics to dicentrics on treatment with radiation, the drug and a combination of the two. The results show that this ratio is markedly influenced by the relative action of the two agents, at low radiation dose, because of the enhancement of the acentric frequency caused by the chemical substance with respect to the spontaneous level. This paper presents the experimental yields of aberrations corresponding to the various treatments, and the calculated frequency ratios of acentrics to dicentrics as a function of X-ray dose, after correction for the physical effect of dose enhancement due to the presence of iodine in the drug.

Chromosome Aberrations↗

Dose-response relationship of radiation-induced harderian gland tumors and myeloid leukemia of the CBA/Cne mouse.

Transplantation of harderian gland cells from CBA/-Cne mice into the fat pad of isogenic recipients was used for a quantitative in vivo study of cell survival and risk of transformation after x-ray irradiation (1-7 Gy). A survival curve for gland cells was generated in vivo with a D0 of 1.83 Gy and an extrapolation number of 7.23. Subsequently, the dose-response curve for lesions observed in nodules after cell transplantation was compared with that for lesions observed in glands irradiated in situ. A high incidence of epithelial hyperplasias with severe dysplasia was observed in transplantation nodules after x-irradiation. Gland tumors were significantly induced in whole-body irradiated animals; the tumors reached a maximum incidence after doses of 3 Gy. The risk of transformation per surviving cell was estimated both for dysplastic lesions and for tumors. These results approximated a dose-squared relationship in both cases, suggesting a common induction mechanism at the cellular level. Myeloid leukemia was observed at all doses in whole-body irradiated mice, and the maximum tumor incidence was reached at doses around 3 Gy.

Animals↗

Radiation-induced mouse liver neoplasms and hepatocyte survival.

Transplantation of hepatocytes from CBA/Cne mice into the fat pads of isogeneic recipients has been used for the quantitative in vivo study of cell survival and risk of transformation after x-ray irradiation (1-7 Gy). A survival curve for liver cells was generated in vivo with a D0 of 3.08 Gy and an extrapolation number not significantly different from 1. Data on liver tumor incidence in whole-body irradiated CBA/Cne and C57BL/Cne X C3H/HeCne (BC3F1) mice are also reported. A statistical analysis of trend in both cases proved a significant induction of tumors by x-rays mainly for doses above 2 Gy. The risk of transformation per surviving cell was estimated for both mouse strains. For CBA mice the data points suggested the presence of a linear component in the dose-effect curve at low doses, whereas for BC3F1 mice a quadratic expression appeared to provide a better description of the points from 1 to 6 Gy. The data of this study suggested that liver tumors can be induced by radiation in mouse strains with either a high or low spontaneous hepatoma incidence.

Animals↗

Influence of age on life shortening and tumor induction after X-ray and neutron irradiation.

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.

Aging↗

Med-fly cell line: response to irradiations with fast neutrons and gamma-rays.

It has been observed that biological systems have different sensitivities to various radiation qualities. Moreover, the relative response depends on the dose level of the applied radiation. In this context the radiosensitivity of Med-fly, Ceratitis capitata Wied., cells, to gamma-rays and neutrons, has been tested by observing cell population growth and mortality. Fast neutron doses ranged between 1.5 and 25 rad, a region of particular interest in radiation protection studies; the 60Co gamma-ray dose values were between 300 and 5 000 rad. The experimental results show a much higher radiosensitivity of these cells to fast neutrons than to gamma-rays, and indicate a dependence of the RBE values on the neutron-dose levels. Furthermore, there was a certain dependence on radiation quality for the morphological damage. Dose-effect relationships are analyzed for both neutrons and gamma-rays and the results are discussed.

Animals↗

Energy deposition by proton beams of up to 31 MeV in microscopic volumes.

The frequency distributions of energy deposition in microscopic volumes for proton beams of various energies and energy spreads were determined by means of a "rossi type" proportional counter. Tissue equivalent spherical volumes of 0.6, 0.72, 0.80, 1.00, 1.25, 1.50, 1.75, 2.00 micrometer diameter were simulated. Frequency distributions of energy deposition per unit pathlength are reported and their behavior as a function of the simulated pathlength, beam energy and energy spread is discussed. The results indicate that energy deposition distributions in microscopic volumes for protons in the range 8-31 MeV are skewsymmetric distributions with a tail on the high energy side, and that degraded beams behave differently from monoenergetic ones. Dose mean lineal energy values have been quoted for beams used in radiobiological experiments.

Protons↗

Dose--effect relationships, r.b.e. and split-dose effects after gamma-ray and fast neutron irradiation of protoplasts from wild Nicotiana species.

Protoplasts from a diploid Nicotiana species were used to investigate the effects of gamma-rays and fast neutrons. The damage was assessed by scoring the relative plating efficiencies. The effects of single acute doses, as well as fractionated doses, are described for both qualities of radiation. The dose--r.b.e. relationship, expressing the effectiveness of fast neutrons relative to gamma-rays as a function of dose, appears similar to that of most animal systems, with higher values in the region of lower doses. The fractionation of gamma-ray doses, with sufficiently long time intervals between split doses, allowed a substantial recovery, as known also for X-rays. On the other hand, the fractionation of a fast neutron dose into low single fractions markedly increased the biological effectiveness of the total dose. This could not be explained by cell progression during resting time intervals and necessitated an additional hypothesis, possibly involving other mechanisms in the specific action of low doses of radiation.

Dose-Response Relationship, Radiation↗

Influence of neutron collimation on the energy deposition in a tissue equivalent sphere.

The influence of neutron collimation on the shape of energy deposition spectra was investigated using a spherical walled proportional counter. Experimental dose averaged lineal energies were obtained and compared with theoretical values. The fractions of total absorbed dose corresponding to various intervals of lineal energies were also deduced from the measured distributions.

Fast Neutrons↗

Neutron scattering and energy deposition spectra.

The influence of neutron scattering in the wall of a spherical proportional counter on the energy deposition spectra and the absorbed dose is investigated. Event probabilities, and frequency and dose-averaged deposited energies are calculated with and without scattering contribution and compared. The change of absorbed dose due to attenuation of the primary neutron flux is also evaluated.

Neutrons↗