Induction of congenital anomalies in offspring of female mice exposed to varying doses of X-rays

Female mice were exposed to varying absorbed doses (108–504 rad) of X-rays and mated at different intervals after irradiation (1–7, 8–14, 15–21 and 22–28 days). Uterine contents were examined at late pregnancy in order to detect early fetal deaths (dominant lethality) and malformations in the live fetuses.Two trends were apparent from data on abnormal fetuses. At each weekly interval, the incidence of abnormalities tended to rise with increase in dose, and, at any given dose, the incidence tended to increase with time after irradiation. Dwarfism and exencephaly were the two most common malformations found.The changes in incidence of dominant lethality and of abnormal fetuses with time and with dose follow each other closely, the highest incidence for both being reached in week 3 (59±4.7% for dominant lethals and 12.5±3.1% for abnormal fetuses, after 504 rad) indicating increased radiosensitivity of less mature oocytes. These results parallel those obtained from known genetic effects reported by other workers and suggest that testing for incidence of congenital malformations among offspring of treated animals may prove a useful means of assessing genetic hazards of radiation of chemicals.     

The induction by X-rays of chromosome aberrations in male guinea-pigs, golden hamsters and rabbits. II. Properties of translocations induced in post-meiotic stages.

Translocations induced by X-rays in post-meiotic germ cells of male guinea-pigs, golden hamsters and rabbits were studied cytologically in the F1 sons of the irradiated males. The percentage of spermatocytes displaying multivalent configurations varied with the translocation, but the average percentage appeared to depend on the species: fewer quadrivalents were observed in hamster than in guinea-pig heterozygotes and most were recorded for rabbit heterozygotes. Chain quadrivalents were more abundant than ring quadrivalents at meiosis for the guinea-pig and hamster, in contrast to the mouse. Too few translocation heterozygotes were examined to determine which meiotic configuration was the more prevalent in the rabbit. In all three species, as in the mouse, translocations were found which caused male sterility, due to partial or complete failure of spermatogenesis, although most translocations caused semi-sterility. For these semi-sterile males both the frequency and time of embryonic death in the progeny appeared to be the same as in the mouse. It is concluded that similar types of chromosome aberrations are induced by X-rays in post-meiotic germ cells of male guinea-pigs, rabbits, golden hamsters and mice.     

The effects of malnutrition on the prenatal development of rat brain]

Female rats were submitted to caloric and protein restriction 8 days before fecondation and during pregnancy. A reduction of the number of brain cells in the fetuses was evident only after the 20th day of pregnancy. This reduction appeared to be limited to glial cells, and not to affect neurons contrarily to what had previously been stated by some authors.     

Time- and dose-dependent biom arker responses in flounder (Platichthys flesus L.) exposed to benzo[a]pyrene, 2,3,3′,4,4′, 5-hexachlorobiphenyl (PCB-156) and cadmium

Responses in flounder (Platichthys flesus) towards benzo [a]pyrene (BaP), 2,3,3′,4,4′,5-hexachlorobiphenyl (PCB-156), and cadmium (Cd) were investigated in time-course and dose-response studies of selected biomarkers. Measurements of biliary fluorescent BaP metabolites and hepatic concentrations of PCB-156 and cadmium showed that the injected toxicants were rapidly m obilized from the muscle to the liver, but a depot effect was indicated in the highest dose groups of BaP and PCB-156 (12 mg kg^-1 bodyweight). Clearest biomarker responses were found in the induction of hepatic cytochrome P450 1A (CYP1A) enzymes as a response towards BaP and PCB-156 exposure. Maximum induction of CYP1A dependent 7-ethoxyresorufin O-deethylase (EROD) activity was observed after 2 and 8 days in BaP and PCB-156-treated flounder, respectively. Positive dose-effect relationships were observed towards both compounds, but the CYP1A induction was more persistent with PCB exposure than with BaP exposure. In Cd-exposed fish, the hepatic level of metallothionein responded more slowly with highest levels observed after 16 days in the time-study. In the combined BaP + Cd treatment, the CYP1A induction was only slightly suppressed. Aspartate aminotransferase in serum appeared to be responsive towards BaP, but also towards the acetone vehicle in controls in the first part of the exposure period. Hematocrit as well as hepatic activities of aldrin epoxidase, glutathione S-transferase, and UDP-glucuronyl transferase were not responsive to any treatm ent in the present study. In general, the results demonstrate that selected biom arkers in flounder are responsive to PAH, PCB, and heavy metal pollutant exposure, indicating the applicability of this species in future environmental pollution monitoring programmes.     

Report From the 39th Annual Meeting of the European Group for Blood and Marrow Transplantation, London, 7–10 April 2013

Antifungal prophylaxis reduces the risks of invasive fungal infection (IFI), all-cause mortality and fungal-related mortality in highly immunosuppressed haemato-oncology patients, but questions remain about the role of therapeutic drug monitoring in this patient population. There is also continuing debate concerning the benefits and risks of empirical versus pre-emptive antifungal therapy when breakthrough IFI occurs during prophylaxis. These topics were discussed during the 39th Annual Meeting of the European Group for Blood and Marrow Transplantation, held in London in April 2013.     

Mechanism of Silver Nanoparticles Action on Insect Pigmentation Reveals Intervention of Copper Homeostasis

Silver nanoparticles (AgNPs), like almost all nanoparticles, are potentially toxic beyond a certain concentration because the survival of the organism is compromised due to scores of pathophysiological abnormalities past that concentration. However, the mechanism of AgNP toxicity remains undetermined. Instead of applying a toxic dose, we attempted to monitor the effects of AgNPs at a nonlethal concentration on wild type Drosophila melanogaster by exposing them throughout their development. All adult flies raised in AgNP doped food showed that up to 50 mg/L concentration AgNP has no negative influence on median survival; however, these flies appeared uniformly lighter in body color due to the loss of melanin pigments in their cuticle. Additionally, fertility and vertical movement ability were compromised due to AgNP feeding. Determination of the amount of free ionic silver (Ag⁺) led us to claim that the observed biological effects have resulted from the AgNPs and not from Ag⁺. Biochemical analysis suggests that the activity of copper dependent enzymes, namely tyrosinase and Cu-Zn superoxide dismutase, are decreased significantly following the consumption of AgNPs, despite the constant level of copper present in the tissue. Consequently, we propose a mechanism whereby consumption of excess AgNPs in association with membrane bound copper transporter proteins cause sequestration of copper, thus creating a condition that resembles copper starvation. This model also explains the cuticular demelanization effect resulting from AgNP since tyrosinase activity is essential for melanin biosynthesis. Finally, we claim that Drosophila, an established genetic model system, can be well utilized for further understanding of the biological effects of nanoparticles.     

Phosphorylation of the Actin Binding Protein Drebrin at S647 Is Regulated by Neuronal Activity and PTEN

Defects in actin dynamics affect activity-dependent modulation of synaptic transmission and neuronal plasticity, and can cause cognitive impairment. A salient candidate actin-binding protein linking synaptic dysfunction to cognitive deficits is Drebrin (DBN). However, the specific mode of how DBN is regulated at the central synapse is largely unknown. In this study we identify and characterize the interaction of the PTEN tumor suppressor with DBN. Our results demonstrate that PTEN binds DBN and that this interaction results in the dephosphorylation of a site present in the DBN C-terminus - serine 647. PTEN and pS647-DBN segregate into distinct and complimentary compartments in neurons, supporting the idea that PTEN negatively regulates DBN phosphorylation at this site. We further demonstrate that neuronal activity increases phosphorylation of DBN at S647 in hippocampal neurons in vitro and in ex vivo hippocampus slices exhibiting seizure activity, potentially by inducing rapid dissociation of the PTEN:DBN complex. Our results identify a novel mechanism by which PTEN is required to maintain DBN phosphorylation at dynamic range and signifies an unusual regulation of an actin-binding protein linked to cognitive decline and degenerative conditions at the CNS synapse.