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P Metalli

Publications and source records attributed to P Metalli.

At least 19 recordsLinked to original sources

Meiotic non-disjunction induced by fission neutrons relative to X-rays observed in mouse secondary spermatocytes. II. Dose-effect relationships after treatment of pachytene cells.

(C57B1/Cne X C3H/Cne)F1 male mice were irradiated with single acute doses of 0.4 MeV neutrons (from 0.11 to 0.72 Gy) or 250 kV X-rays (from 0.25 to 3 Gy) and sacrificed 5 days later. Chromosome preparations of secondary spermatocytes, irradiated at the stage of pachytene, were analysed and the incidence of hyper-haploidies and chromosome fragments was recorded. Data on numerical aberrations were fitted by highly significant linear relationships for both types of radiation. A relative biological effectiveness (RBE) value of 5.65 was estimated by the ratio between the slopes of the two regression lines. The same linear fitting was applied to frequencies of cells with fragments, even if in this case other types of functions could not be excluded. An RBE value was estimated in the same way as for numerical aberrations and yielded a comparable figure of 5.23. A significant correlation was also found between the incidence of numerical and structural aberrations, which points to the chromosome itself as the prevalent target for radiation-induced non-disjunction (ND). In addition, the highly significant linearity of the dose-effect relationship observed for the induction of aneuploidies suggests, as the simplest hypothesis, a single-hit mechanism of radiation action, possibly through pre-non-disjunctional damage to the centromeric region, rather than an indirect induction of segregational difficulties after primarily induced chromatid interchanges.

Aneuploidy↗

Nondisjunction induced in mouse spermatogenesis by chloral hydrate, a metabolite of trichloroethylene.

The effects of chloral hydrate (CH), an in vivo metabolite of trichloroethylene, have been evaluated by cytogenetic observations of mouse secondary spermatocytes after ip treatment with 82.7, 165.4, or 413.5 mg/kg bw. Hyper-haploid metaphases have been scored to determine whether previous observations in various nonmammalian organisms about an effect of this drug on the mitotic spindle could be confirmed in mice. At each dose, the frequencies of hyper-haploid cells have been estimated to assess the response of pachytene, preleptotene, premeiotic, and staminal gonial cells. Significant increases above the control value have been observed particularly after treatment of actively dividing gonial cells, confirming the results obtained with the same batch of the drug in a parallel collaborative investigation with Aspergillus nidulans. Thus: a) chloral hydrate has been shown to be effective in inducing nondisjunction in a mammalian system; b) a prevalent action on the mitotic spindle has been confirmed and quantified; and c) the usefulness of parallel investigations with different methods is stressed, particularly to collect information about the mechanisms of induction of nondisjunction events.

Animals↗

Reciprocal translocations in ageing mice and in mice with long-term low-level 239Pu contamination.

Single intravenous injections of 185 Bq monomeric 239Pu were given to male mice, and the frequency of primary spermatocytes with reciprocal translocations, determined 724 days after treatment, was not significantly different from that of age-matched untreated controls. These old animals showed significantly higher aberration frequencies than young adults. The data therefore show that for low initial activity and very long retention time the possible cytogenetic effects of incorporated nuclide does not change the age-related pattern of increase of spontaneous chromosome aberrations. Considerations of the main variables involved in the induction of cytogenetic effects of incorporated plutonium, based on literature data, indicate that the initial injected activity, the estimated total accumulated average organ dose, and the retention time interact in a complex way; as far as can be seen at present, the effects seem to be dependent mainly on the initial activity at short times after contamination, while the retention time appears to be predominant in the case of long-term observations.

Aging↗

Cell and cell-free transplantation experiments with a mouse reticulum cell sarcoma.

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.

Animals↗

Role of the spleen in spontaneous reticulum cell sarcoma of (C57BL/Cne x C3H/Cne)F1 mice.

(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.

Age Factors↗

Dose-incidence variations of reticulum cell sarcoma in mice with irradiated bone marrow.

The average final incidence of reticulum cell sarcoma (RCS) in untreated control (C57BL/Cnefemale X C3H/Cnemale)F1 male mice was 57% and was not significantly changed by single acute whole-body doses of X-rays up to 400 rads. Higher doses sharply decreased this incidence to very low levels. In a syngeneic chimera system, however, irradiation (400 rads) of bone marrow prior to transplantation significantly increased the frequency and rate of RCS relative to transplantation of unirradiated marrow. An endogenous repopulating system was tested; marrow was irradiated in situ by a limb-shielding technique. The results indicated a biphasic dose-incidence curve with a peak at 500 rads. The rising part of the curve was in agreement with and extended the conclusion from the exogenous system, whereas the descending portion at higher doses paralleled the trend observed in the whole-body X-irradiated animals. Finally, the irradiation of two hind legs resulted in a higher frequency of RCS than did irradiation of only one leg at the same dose levels.

Animals↗

Late somatic effects in syngeneic radiation chimaeras. III. Observations on animals repopulated with irradiated marrow.

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.

Animals↗

Observations on late effects in mice exposed to 400 MeV neutrons.

Life-long observations on mortality and pathology at death were carried out on groups of mice irradiated with 250 kV X-rays or exposed to a 400 MeV neutron beam, both directly and after attenuation corresponding to the maximum dose build-up region, at comparable dose-rates. Doses up to 84 rad of 400 MeV neutrons and up to 200 rad of X-rays showed no effect on the longevity of the animals, which suggest an upper limit to the r.b.e. for life-shortening of approximately 2-5. Similar conclusions were drawn from the data on all types of leukemias. For all other neoplasms, the age-specific death-rate showed a similar shortening of the latency times for groups of mice irradiated with 0-84 rad of 400 MeV direct neutrons and 0-400 rad of X-rays, also suggesting an upper limit to the r.b.e. slightly higher than that previously indicated for life-shortening. No definite effect was observed after exposure to the attenuated neutron beam at the doses used in these experiments.

Animals↗

Immune responsiveness and incidence of reticulum cell sarcoma in long-term syngeneic radiation chimeras.

Long-term syngeneic radiation chimeras displayed a very low incidence of reticulum cell sarcoma as compared with control mice. Immune reactivity of these animals was studied in vivo by anti-dinitrophenyl antibody titer and affinity and in vitro by mitotic responsiveness to phytohemagglutinin, concanavalin A and lipopolysaccharide. Anti-body titer and affinity as well as the response to T lectins were found to be increased in chimeras. These results were attributed to increased function of mature T2 cells, which could explain the reduced incidence of reticulum cell sarcoma in chimeras.

Animals↗