Study of the structure and metabolism of the rat thymus gland during long-term administration of tritium oxide in different doses

During-3-month administration of tritium oxide (0.37, 0.925 and 1.85 MBq/g body weight) to rats one could observe the loss of the thymus weight, decrease in the concentration, content and production of DNA and RNA per organ, reduction of the molecular weight of single-stranded DNA, increase in the content of the salt-soluble polydeoxyribonucleotides, and activation of acidic DNAases. These changes were function of tritium dose daily administered to rats.     

Comparative evaluation of the carcinogenic effects of chronic exposure to tritium oxide and external gamma-radiation

In experiments of on rats a study was made of late effects of chronic action of tritium oxide (3HOH) during 6 months (37 X 10(4) Bq/g/day) and external gamma-radiation (137Cs) which were delivered in comparable daily and cumulative doses. It was shown that 3HOH produced a more pronounced blastomogenic effect. The RBE coefficient of tritium oxide approximated 1, with a reference to the average life shortening, and 4.2 and 2.5, with a reference to the incidence of malignant tumors and leukoses, respectively.     

Comparison of the biological effects of tritium oxide and gamma radiation based on changes in the mass of the rat thymus gland

RBE of tritium oxide (cumulative doses from 0.33 to 14.7 Gy), in comparison with gamma-radiation, amounted to 2-3 as estimated by the thymus mass. As determined by the rate of injury and repair, the RBE values decreased from 4 to 1.4 with dose increasing, and from 6.5 to 1.3, by the periods of half-decrease and half-recovery of the organ mass. The 2-3-fold variations in the RBE values for various parameters of the organ mass changes were registered at low doses, whereas within the range of median and high doses under study, the differences were insignificant.     

Relative biological effectiveness of tritium oxide based on DNA destruction and thymus depletion in rats

As estimated by DNA destruction and thymus depletion for 21 days of observation, relative biological effectiveness (RBE) of tritium oxide (RBE HTO), as compared to gamma-quanta (137Cs), was 3.1 +/- 0.2 and 3.1 +/- 0.3, respectively. On days 1, 3, 7, 10, 14, and 21 RBE HTO, for the same indices at minimum radiation doses, was about 6-2. As determined by T1/2 period of double-stranded DNA diminution and thymus cell depletion RBE HTO was 5.5 +/- 0.4.     

Role of rat thymus chromatin lipids in response to the harmful effect of gamma-radiation

In vitro incubation of thymocytes with [2-14C]acetate results in a more intensive label incorporation into chromatin lipids as compared to nuclear lipids. The deleterious effect of gamma-irradiation leads to specific changes in [2-14C]acetate incorporation into the total fraction of phosphatidylcholine-phosphatidylserine and chromatin sphingomyelin. This is paralleled with an increase in the ratio of specific radioactivities of chromatin cardiolipin and nuclear cardiolipin. The changes in specific radioactivities of sphingomyelin, phosphatidylcholine-phosphatidylserine and cardiolipin suggest a role of phospholipids in the mechanisms of regulating the activity of intranuclear structures.     

AP-PCR assay of DNA alterations in the progeny of male mice exposed to low-level gamma-radiation

By comparative analysis of fingerprints of arbitrarily primed polymerase chain reaction (AP-PCR) products, DNA alterations in somatic cells of the progeny (F1 generation) of male mice chronically exposed to low-doses of gamma-radiation was investigated. Male BALB/c mice exposed to 10-50 cGy were mated with unirradiated females 15 days after irradiation. DNA was isolated from biopsies taken from tail tips of 2-month-old progeny. Preliminary AP-PCRs were carried out with 17 primers representing core sequences of micro- and/or minisatellites or their flanking oligonucleotides. Best quantitatively reproduced AP-PCR fingerprints of genomic DNA were obtained with one of these primers, a 20-mer oligonucleotide flanking the micro-satellite locus Atplb2 on mouse chromosome 11. Comparative analysis of individual fingerprints of AP-PCR products obtained on DNA templates from the progeny of irradiated and intact males revealed an increased variability of micro-satellite-associated sequences and an increased frequency of "non-parental bands" in DNA-fingerprints from the progeny of males chronically exposed to gamma-radiation 15 days before mating (at the postmeiotic stage of spermatogenesis). The results show that increased micro-satellite instability can be initiated by irradiation of the male parent to subsequently arise or be transmitted to the soma of the F1 generations.     

Nucleic acid metabolism in rat hematopoietic tissues during and after prolonged administration of different doses of tritium oxide

During the long-term administration to rats of tritium oxide in doses of 0.37, 0.925 and 1.85 MBq/g body mass the content of karyocytes and nucleic acids in the bone marrow and spleen was decreased, the rate of their biosynthesis changed, the DNA structure impaired, the content of salt-soluble polydeoxynucleotides increased, and DNAases activated. The observed changes were function of dose. After the end of the administration of the isotope the animals which had received a lesser tritium dose exhibited a more rapid and complete recovery.     

Incorporation of tritium into the DNA of hematopoietic tissues during prolonged administration of tritium oxide

With long-term (90 days) administration of tritium oxide (0.37 MBq/g body weight) to ras the carbon-bound tritium accumulated in DNA of haemopoietic tissues during two-month administration of the isotope (the accumulation half-time of 15-25 days); during the next month, the isotope level remained nearly constant (about 20 X 10(6) decay/min/g DNA). Elimination of tritium from DNA started 3 days after termination of its administration and proceeded with two half-times (4-8 days and 12-18 days). The ratio of the tritium content per 1 M hydrogen of DNA to tritium content per 1 M hydrogen of tissue water increased up to 0.5-0.7 during the uptake of tritium oxide, and up to 4-7 after the administration of the isotope had ceased.     

Comparison of UV-induced unscheduled DNA synthesis in lymphocytes exposed to low doses of ionising radiation in vivo and in vitro

In an attempt to understand and ascertain the stimulatory effects of low-dose ionising radiation, a study was conducted to compare the changes in the UV-induced repair capacity of human blood cells exposed to low conditioning doses of ionising radiation under in vivo and in vitro conditions. A significant increase in the rate of UV induced Unscheduled DNA synthesis (UDS) in lymphocytes pre-exposed to low doses of ionising radiation was observed both under in vitro and in vivo conditions. There was also a significant correlation between the adapting dose and net UDS in lymphocytes of radiation workers implying that the triggering action of the adaptation process is dose dependent. However, on comparing the extent of UV-induced UDS of the in vivo and in vitro exposures, significantly higher rates of UDS were observed in the lymphocytes of radiation workers when compared to a corresponding in vitro adapting dose. We postulate that the response in vivo is much more pronounced due to cell repopulating events and extra cellular secretory factors like hormones etc,.     

Effect of super-high doses of gamma-radiation on the level and metabolism of serotonin in the rat brain

As early as 60 mi after gamma-irradiation of Wistar rats with a dose of 150 Gy the content of serotonin and 5-hydroxyindoleacetic acid decreases in the midbrain, hippocampus, and cerebral hemisphere cortex. The decrease is most pronounced in the midbrain where serotoninergic neurons are located. The changes are accumulated during the first 24 h following irradiation.     

Nucleic acid metabolism in rat liver after single and prolonged exposure to tritium oxide

It was shown that after a single administration of tritium oxide in a dose of 22.2 MBq/g body mass the liver mass increased, the concentration of nucleic acids decreased and the biosynthesis rate increased during a one-month observation. By the end of the observation period (the first year) the parameters under study were normalized. The long-term administration of tritium oxide in daily doses of 0.37, 0.925 and 1.85 MBq/g body mass caused changes in the nucleic acid metabolism which were less manifest (at early times), than in the case of a single injection. At the same time, the long-term administration of tritium oxide in the dose of 0.925 MBq/g caused a substantial disturbance of the nucleic acid metabolism at later times (after 2-9 months).     

Characteristics of osteosarcomas and morphological changes in the rat thymus during the combined action of gamma-radiation and 239Pu

Under the combined effect of external gamma-irradiation and 239Pu, osteosarcomas occur more frequently and at earlier times, and have more pronounced multicentric pattern of growth and metastatic spreading than occurs with the two agents delivered separately. The difference is in the increased development of tumors and the decreased osteogenesis. Tumor carriers develop atrophy of thymus lymphoid tissue more frequently than normal ones.     

DNA damage and repair in embryonic mouse limbs exposed to teratogenic doses of methylnitrosourea

The alkaline elution assay was used to monitor DNA single-strand breaks in embryonic tissue following exposure to the DNA-damaging teratogen N-methyl-N-nitrosourea (MNU, CAS No. 694-93-5). An animal model was developed in which nearly every fetus exposed to the highest dose of MNU had malformations of the hindlimbs while the fetuses exposed to the lowest dose of MNU had none. Hindlimbs pooled within litters were analyzed for DNA single-strand breaks by alkaline elution conducted at rapid (0.35 ml/min) and slow (0.35 ml/min) speeds. Breaks in the DNA of hindlimbs exposed to teratogenic doses of MNU were readily detected by alkaline elution only if slower speeds were used in the assay. Using the more sensitive procedure, DNA breakage was monitored over a 24-h period. DNA breakage peaked in the MNU-exposed hindlimbs in a dose-dependent manner 4 h after injection. While the elution profiles of hindlimbs exposed to the lower doses of MNU returned to control levels 8 h after injection, single-strand breaks persisted in the hindlimbs exposed to the highest dose of MNU for at least 20 h. These latter data suggest that the highly teratogenic dose of MNU induced DNA damage that was more slowly repaired than that produced at lower doses, possibly by saturation of DNA repair systems. Although some necrosis did occur in hindlimbs exposed at teratogenic dose levels, it was not severe and it did not appear to influence the alkaline elution results. These experiments show that alkaline elution is a sensitive assay for the detection of DNA damage in embryonic tissues.     

DNA damage in Chinese hamster cells repeatedly exposed to low doses of X-rays

In a recent paper we reported the results of an experiment carried out by analysing chromosomal damage in Chinese hamster (CHO) cells exposed to low doses of X-rays. The present investigation was undertaken in order to validate those results using a different approach, the single cell gel electrophoresis assay (comet assay) immediately after irradiation. Cells were cultured during 14 cycles, irradiation treatment was performed once per cycle when the cells were at 90-95% of confluence. Doses of 2.5, 5.0 and 10.0 mSv were used. Sequential irradiation of CHO cells induced a decrease of cells without migration and an increase of cells showing DNA damage with the three doses employed. Significant increases of low-level damaged cells (p < 0.001) were found for the 14 exposures when compared to controls except for the first irradiations with 2.5 and 10 mSv, respectively. No significant increase of the frequency of cells with severe damage was observed in any case. These findings could be explained by assuming a complex interactive process of cell recovery, DNA damage and repair together with the induction of genomic instability, the incidence of bystander effects as well as some kind of radioadaptative response of the cells. If these phenomena are limited to the cell line employed deserves further investigation.     

Morphofunctional status of the thymus in guinea pigs exposed to thymus and bone marrow preparations

Study of the effect of the polypeptide thymic factor (thymalin) and the polypeptide bone marrow factor (hemalin) on the morphofunctional status of the thymus in guinea-pigs has shown that injection of thymalin into animals increases the count of small lymphocytes whereas injection of hemalin the count of medium-sized lymphocytes and lymphoblasts. Injection of thymalin magnifies the size of the nuclei of the reticuloendothelial cells.     

Comparison of the effect of gamma-radiation and fast neutrons on the biosynthesis of DNA in rat bone marrow in different stages of proliferation

In experiments with rats of different age exposed to gamma- or neutron-radiation it was shown that in younger animals, the inhibition of DNA synthesis in the bone marrow was of a lesser degree but more stable without a tendency toward recovery. Inhibition of DNA synthesis was more pronounced in mature rats, but in 18 h it was completely or partially eliminated. Neutrons of 1.5-2 MeV caused a more pronounced, than gamma-radiation, inhibition of DNA synthesis in all animals under study irrespective of their age: the inhibition was similar in animals with different levels of bone marrow proliferation.