The neuropathology of trimethyltin in the marmoset (Callithrix jacchus) hippocampal formation.

The effects of single and repeated doses of trimethyltin (TMT) treatment on the central nervous system (CNS) of the marmoset were investigated. For the acute-dose experiment adult animals were administered 3 mg/kg of TMT chloride (ip) and were then observed for changes in behavior. Within 24 hr postinjection all animals developed tremors, ataxia, and unresponsiveness. Half of the animals had severe clinical deterioration and died at 2 to 3 days following treatment. Surviving marmosets were sacrificed and the brain was subsequently perfusion-fixed for light microscopic examination. Neuronal degeneration was observed in many cells of the Ammon's horn and fascia dentata of the hippocampus. For the chronic-dose experiment, adult marmosets received (ip) weekly doses of 0.75 mg/kg of TMT chloride for 24 weeks. No evident clinical signs or behavioral changes were observed in any of the treated animals. Histological examination revealed neuropathological changes comparatively similar but less severe than those observed in the acute-treated animals. The differences in toxicity effects between acute and chronic TMT administration are compared and discussed.

Damage and repair of mouse bronchial epithelium following acute inhalation of trichloroethylene.

The time-course of damage and repair in the bronchial epithelium of the mouse was studied morphometrically after a single inhalation of trichloroethylene (TCE). Mice were exposed for 30 min to 500, 1000, 2000, 3500, or 7000 ppm of TCE under controlled conditions and sacrificed after 2 and 24 h, and 2, 5, and 7 days. At all TCE concentrations, the damage consisted of dilation of endoplasmic reticulum and was selective for nonciliated cells throughout the bronchial tree. Damage was quantitatively evaluated by counting the percentage of vacuolated cells. Injury was maximal 24 h after exposure and was significantly (p less than 0.05) higher in bronchi with a diameter smaller than 0.4 mm (67.0% +/- 8.5%) in comparison with larger bronchi (34.0% +/- 13.2%). Cell turnover was studied by autoradiography after [3H]thymidine injection. Following TCE inhalation, the percentage of [3H]thymidine labeled cells, which in the controls was virtually zero, increased to a maximum of 13.5% +/- 6.8% (average at all doses) 48 h after treatment and then rapidly decreased to baseline values at 7 days (0.2% +/- 0.1%). Repair of some cells occurred after 24 h, and at 48 h the percentage of vacuolated cells decreased and became significantly related (p less than 0.01) to the administered TCE dose (2.4% +/- 1.4% and 21.2% +/- 6.0% average in the 500 and 7000 ppm groups, respectively). Repair of bronchial epithelium took place by both recovery of less damaged cells and proliferation of residual nonciliated cells, leading to restoration of the normal ratio between ciliated and nonciliated cells.

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.

Long-term 238Pu and 239Pu retention and organ distribution in mice at low doses.

The 238Pu and 239Pu distribution in femur, liver, kidneys and testes and the retention function in the skeleton and liver have been studied in about 50 (C57 BL X C3H) F1 male mice. Groups of about 5-10 male mice were sacrificed from 10 to 800 days postinjection to cover their entire life span. All animals were injected intravenously with monomeric solutions of plutonium (1% trisodium citrate at pH 6.5) at doses of the order 7-15 kBq/kg body weight. The low levels of plutonium have been measured by direct counting in the entire animals and by radiochemical methods in the various tissues and organs. Significant differences between 238Pu and 239Pu were not observed at the injected doses used. The following proportions of the injected doses are retained in mice at the end of their life span: 12% in the skeleton, 0.7% in the liver, 0.1% in kidneys and 0.06% in gonads. Furthermore, the data have shown that (1) the long-term component of the plutonium skeleton retention in mice has a biological half-time that is much longer than their average life span; and (2) the long-term component of the plutonium liver retention in mice has a biological half-time of about 350 days.

The relationship between o.e.r., r.b.e. and number of fractions for X-ray- or neutron-induced skin damage.

The skin reactions in aerated and hypoxic mouse tails after single or fractionated doses of 250 kV X-rays or fast neutrons (6 MeV deuterons on beryllium) have been measured. The o.e.r. for one to sixteen fractions of X-rays remains constant, while that for one to ten fractions of neutrons decreases with increasing neutron fractionation and decreasing neutron dose/fraction. The o.e.r. for X-rays was 1.7, for single-neutron doses 1.4, and for ten fractions of neutrons 1.25. It was anticipated that the o.e.r. for neutron-induced damage would decrease further as neutron fractionation is increased because the contribution to damage from the highest LET components of dose, the alpha and heavy recoil particles, would increase relative to the lowe LET components. The r.b.e. values obtained for skin damage were higher at all neutron doses/fraction examined in this study on tails than all those previously obtained in studies on skin at other sites on four species. This may be due to the influence of hypoxia on the r.b.e. measurements in the mouse tail.

Sublethal damage in cells of the mouse gut after mixed treatment with X rays and fast neutrons.

The effect of combining X ray and neutron irradiations on cell survival in the mouse intestine has been investigated. The irradiations from the two beams were given within minutes or at most a few hours of each other when recovery from sublethal damage was not always complete. The results show that cells surviving the first dose of radiation have accumulated the same amount of recoverable sublethal damage regardless of whether that first dose was with X rays or neutrons. The rate at which the sublethal damage is shed is the same after X rays or neutrons. It is reasoned that there is less sparing of damage by fractionation of neutron dose compared with fractionation of X ray dose not because there is less recovery from sublethal damage after neutrons but because there is relatively more lethal damage; the recovery from any sublethal damage is the same as if it were from X rays. If X rays and neutron doses are separated by times long enough to allow the full repair of sublethal injury then the combined effect is simply additive.

The role of the spleen in the repopulation of the haemopoietic system of heavily-irradiated mice.

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.

Amniotic fluid surface tension during pregnancy.

A good correlation between the amniotic fluid surface tension and gestational age was found in 51 amniotic fluid samples from normal pregnancies. The samples were obtained between the 20th and 43rd week of gestation. A good relation also exists between amniotic fluid lecithin concentration and fluid surface tension, and between said surface tension and the foam test carried out according to Clements et al. (4).