Effects of low radiation doses on Chinese hamster cells

The induction of cytogenetic damages after irradiation with single dose of gamma-rays (0.1-2 Gy) have been studied. It is shown non-linear curve for the induction of chromosome aberrations, detected by anaphase method. After irradiation in S-stage of the cell cycle at dose below 0.2 Gy the cells were more radiosensitive than after irradiation with doses 0.3-2 Gy. Between the phases of high radiosensitivity and radioresistance the reversal dose-effect relation was observed. This phenomenon was not marked for the cells after irradiation in G2-stage of the cell cycle. It is possible, this results could reflect an induced radioresistance at low dose of irradiation.     

Effect of very low doses of gamma radiation on motility of gill ciliated epithelia of Mytilus edulis

An investigation of the effect of gamma radiation on the motility of mussel gill ciliated epithelia was conducted using dose rates of 0.9 and 2 mGy/h. There was a definite decrease in the beat frequency and a distortion of the metachronal wave by 20-30 min after irradiation with 0.9 Gy/h. With a total dose of 0.9 mGy, the beat frequency was decreased 2- to 2.5-fold. In the period after irradiation a restoration of the metachronal wave was observed, but the beat frequency was about 50% of the control level. Gamma irradiation completely stopped the beating of the cilia when given at a dose rate of 2 mGy/h.     

Prooxidant link of oxidative homeostasis under low doses of ionizing radiation of low intensity

Peculiarities of the processes of lipids peroxidation under effect of ionizing radiation in small doses and its low intensity have been considered. Data from literature concerning the threshold doses of lipids peroxidation activation have been generalized.     

Molecular cloning and immunologic reactivity of a novel low molecular mass antigen of Mycobacterium tuberculosis

Polypeptide Ags present in the culture filtrate of Mycobacterium tuberculosis were purified and evaluated for their ability to stimulate PBMC from purified protein derivative (PPD)-positive healthy donors. One such Ag, which elicited strong proliferation and IFN-gamma production, was further characterized. The N-terminal amino acid sequence of this polypeptide was determined and used to design oligonucleotides for screening a recombinant M. tuberculosis genomic DNA library. The gene (Mtb 8.4) corresponding to the identified polypeptide was cloned, sequenced, and expressed in Escherichia coli. The predicted m.w. of the recombinant protein without its signal peptide was 8.4 kDa. By Southern analysis, the DNA encoding this mycobacterial protein was found in the M. tuberculosis substrains H37Rv, H37Ra, Erdman, and "C" strain, as well as in certain other mycobacterial species, including Mycobacterium avium and Mycobacterium bovis BCG (bacillus Calmette-Guerin, Pasteur). The Mtb 8.4 gene appears to be absent from the environmental mycobacterial species examined thus far, including Mycobacterium smegmatis, Mycobacterium gordonae, Mycobacterium chelonae, Mycobacterium fortuitum, and Mycobacterium scrofulaceum. Recombinant Mtb 8.4 Ag induced significant proliferation as well as production of IFN-gamma, IL-10, and TNF-alpha, but not IL-5, from human PBMC isolated from PPD-positive healthy donors. Mtb 8.4 did not stimulate PBMC from PPD-negative donors. Furthermore, immunogenicity studies in mice indicate that Mtb 8.4 elicits a Th1 cytokine profile, which is considered important for protective immunity to tuberculosis. Collectively, these results demonstrate that Mtb 8.4 is an immunodominant T cell Ag of M. tuberculosis.     

The effect of gamma radiation at low doses on the receptor binding of triiodothyronine in the nuclei of rat liver cells

Subacromial bursal specimens from 63 patients undergoing surgery for rotator cuff tearing (n = 43), the impingement syndrome (n = 14), and calcifying tendinitis n = 6) were studied to characterize the reactions that develop at the tendinopathy "lesional" sites. Intensity of the bursal reactions and production of type III collagen vary considerably, with the highest incidence of both seen in patients with rotator cuff tears. The intensity of bursal reactions correlated with the degree of formation of perivascular new collagen and type III collagen expression. In 22 of the 63 patients the bursal reaction distant to the tendon lesion was also studied. It was minimal and did not correlate to the lesional bursal findings. A strong correlation, however, existed between surgical appearance and histologic grading. The term "localized bursal reaction" as opposed to bursitis more correctly describes bursal involvement. Resection of bursal tissues should be limited to the lesional tissue that interferes with subacromial motion.     

Effects of low doses of ionizing radiation and induced hypothyroidism on the course of pregnancy and the development of the offspring in rats

OBJECTIVES: To determine the appropriate indications and timing for surgery in children with either a perimembranous or a subarterial type of ventricular septal defect (VSD) associated with aortic cusp prolapse. DESIGN: Retrospective review of children with VSD and associated aortic cusp prolapse with or without aortic regurgitation. This review was based on data obtained from clinical findings, two-dimensional echocardiography, cardiac catheterization and angiocardiography. SETTING: Tertiary health care facility with two-dimensional and colour Doppler echocardiographic and cardiac surgery facilities, and a catheterization laboratory. PATIENTS: Forty-eight patients were found to have perimembranous or subarterial VSDs in association with aortic cusp prolapse with or without aortic regurgitation. INTERVENTIONS: All 48 patients had high resolution two-dimensional and colour Doppler echocardiography. Of the 19 patients who underwent surgical closure of their VSD, five also had an aortic valvuloplasty and one had an aortic valve replacement. Cardiac catheterization was performed in 16 of the 19 surgical patients and 12 of the 29 nonsurgical patients. MEASUREMENTS AND MAIN RESULTS: Annual clinical and echocardiographic assessments in the nonsurgical group did not demonstrate increasing aortic insufficiency. Two children in the nonsurgical group showed spontaneous resolution of aortic insufficiency. In the surgical group, four children with VSD and clinical aortic insufficiency had surgery at less than five years of age; two were found to be regurgitant-free, one had trivial clinical aortic insufficiency and the other had echocardiography-only insufficiency. Of the seven surgical patients older than five years with VSD and clinical aortic insufficiency, four were found to be regurgitant-free, one had echocardiography-only regurgitation and two were unchanged. Two children undergoing surgery with VSD and no aortic insufficiency had postoperative echocardiography-only regurgitation, presumably related to cusp deformity from presurgical prolapse. Children with large VSDs with or without aortic cusp prolapse required surgery for indications of shunt size and pulmonary resistance. CONCLUSIONS: For children with small perimembranous VSDs and cusp prolapse, surgery is indicated only if there is clinical evidence of aortic regurgitation and progressive left ventricular enlargement.     

Pulmonary carcinogenicity of relatively low doses of beta-particle radiation from inhaled 144CeO2 in rats

This study was conducted to examine the carcinogenic effects of inhaled beta-particle-emitting radionuclides, particularly in lower dose regions in which there were substantial uncertainties associated with available information. A total of 2751 F344/N rats (1358 males and 1393 females) approximately 12 weeks of age at exposure were used. Of these, 1059 rats were exposed to aerosols of 144CeO2 to achieve mean desired initial lung burdens (ILBs) of 18 kBq (low level), 247 rats to achieve mean ILBs of 60 kBq (medium level) and 381 rats to achieve mean ILBs of 180 kBq (high level). Control rats (total of 1064) were exposed to aerosols of stable CeO2. Based on the 95% confidence intervals of the median survival times and the cumulative survival curves, there were no significant differences in the survival of groups of female and male exposed rats relative to controls. The mean lifetime beta-particle doses to the lungs of the rats in the four groups were: low level, 3.6 +/- 1.3 (+/-SD) Gy; medium level, 12 +/- 4.5 Gy; and high level, 37 +/- 5.9 Gy. The crude incidence of lung neoplasms increased linearly with increasing doses to the lungs (controls, 0.57%; low level, 2.0%; medium level, 6.1%; and high level, 19%). The estimated linear risk coefficients for lung neoplasms per unit of dose to the lung were not significantly different for the three dose levels studied. The risk coefficient at the lower level was 39 +/- 14 (+/-SE) excess lung neoplasms per 10(4) rat Gy; at the medium level the risk was 47 +/- 12; and at the higher level the risk was 50 +/- 9.0. The relationship of beta-particle dose to the lung and the crude incidence of lung neoplasms was described adequately by a linear function. We concluded that the risk of lung neoplasms in rats per unit of radiation dose did not increase with decreasing mean beta-particle dose to the lung over the range of 3.6 to 37 Gy. The weighted average of these three values was 47 +/- 6.4 (+/-SE) excess lung neoplasms per 10(4) rat Gy. To extend the risk coefficients for lung neoplasms to lower doses by experimentation will require much larger numbers of rats than used in this study.     

Structural changes in membranes of proliferating leukocytes L-41 as affected by low doses of ionizing radiation

The dose-dependent effects of gamma-radiation on the leucocyte cultures L-41 has been investigated. Irradiation by the dose of 0.25 Gy stimulates the cell proliferation while that by the doses of 1.0 and 2.0 Gy inhibits this process. In this dose range the radiohormesis effects characterizing structural organization of the probed membranes have been also registered for fluorescence parameters. The zone of qualitative transition of response of the cell membranes to radiation is individual for various effects. The action of radiation in the doses of 0.25 and 0.50 Gy induces a decrease of ANS fluorescence intensity and a decrease of membrane protein immersion in the lipid bilayer of leukocyte membranes. The values of these parameters rise at the doses of 1.0 and 2.0 Gy that reflects different directions of structural changes in various membrane regions. The irradiation in the range of 0.25-1.0 Gy induces the increase of microviscosity in deep regions of membrane lipid matrix while at the dose 2.0 Gy it causes its decrease. Radioactive radiation does not change the membrane protein conformation of leukocytes and polarity of lipid bilayer hydrophobic zones as recorded by fluorescent methods used.     

DNA excision repair as a component of adaptation to low doses of ionizing radiation in Escherichia coli

The effects of chronic lithium chloride infusions on consumption of, and subsequent preferences for, a novel diet were examined in rats with ablations of the area postrema (AP) and sham-lesioned control rats. Osmotic minipumps (Alza), filled with a saturated aqueous solution of LiCl (63 g/100 ml), were implanted in the peritoneal cavity of half of the lesioned rats (n = 9) and half of the control rats (n = 8). The remaining rats received empty pumps (n = 9 and n = 7 for lesioned and controls, respectively). The LiCl or sham drug phase was paired with free access to a highly palatable novel diet (AIN diet) during a 7-day conditioning period. Subsequent preferences for the novel diet relative to a familiar diet (ground Purina lab pellets) were determined using a two-food choice procedure. The only group to show a persistent and significant reduction in novel food consumption during the conditioning phase was the sham-lesioned group infused with LiCl (p < 0.01). This group also exhibited a marked aversion for the novel diet, indicative of a conditioned food aversion (CFA), during the preference tests. No significant differences in novel diet consumption or in novel diet preference were found between the two AP-lesioned groups. This study provides evidence that anorexia and CFAs to a novel diet, induced with chronic infusions of lithium, are abolished by destruction of the chemosensitive area postrema.     

A longitudinal study of immunologic reactivity in leprosy patients treated with immunotherapy

More than 150 leprosy patients treated with multidrug therapy (MDT) plus immunotherapy (IMT) with a mixture of heat-killed Mycobacterium leprae plus live BCG were studied in relation to humoral and cell-mediated immune responses. Many previously had received prolonged sulfone monotherapy. Patients received 2 to 10 doses of IMT in a period of 1 to 3 years, depending upon their clinical form of leprosy. The patients were followed up for 5 to 10 years with repeated determinations of antibody levels to phenolic glycolipid-I; lymphoproliferative (LTT) responses to soluble extract of M. leprae, to whole bacilli and to BCG, skin-test responses and bacterial indexes (BIs). After MDT plus IMT there was a statistically significant decrease of antibody levels in the multibacillary (MB) group. The BI decreased proportionally to the ELISA results. LTT increased to M. leprae antigens, especially to soluble extract, in a high percentage of these patients (34% of LL patients positive). Lepromin positivity in MB patients increased from 5% initially positive to 75% at the cut-off during this follow up. These results show substantial early and persistent cell-mediated reactivity to M. leprae in many MB patients treated with MDT-IMT, confirming and expanding previously published data.     

Patient radiation doses during cardiac catheterization procedures

The objective of the present project was the determination of the dose received by patients during cardiac procedures, such as coronary angiography, percutaneous transluminal coronary angioplasty (PTCA) and stent implantation. Thermoluminescent dosemeters (TLDs), suitably calibrated, were used for the measurement of the dose received at four anatomical locations on the patient's skin. A dose-area product (DAP) meter was also used. The contribution of cinefluorography to the total DAP was higher than that of fluoroscopy. A DAP to effective dose conversion factor equal to 0.183 mSv Gy-1 cm-2 was estimated with the help of a Rando phantom. Thus, the effective dose received by the patients could be assessed. Mean values of effective dose equal to 5.6 mSv, 6.9 mSv, 9.3 mSv, 9.0 mSv and 13.0 mSv were estimated for coronary angiography, PTCA, coronary angiography and ad hoc PTCA, PTCA followed by stent implantation and coronary angiography and ad hoc PTCA followed by stent implantation, respectively.     

Estimation of radiation absorbed doses to the red marrow in radioimmunotherapy

Myelotoxicity is the dose-limiting factor in radioimmunotherapy. Traditional methods most commonly used to estimate the radiation adsorbed dose to the bone marrow of patients consider contributions from radionuclide in the blood and/or total body. Targeted therapies, such as radioimmunotherapy, add a third potential source for radiation to the bone marrow because the radiolabeled targeting molecules can accumulate specifically on malignant target cells infiltrating the bone marrow. A non-invasive method for estimating the radiation absorbed dose to the red marrow of patients who have received radiolabeled monoclonal antibodies (MoAb) has been developed and explored. The method depends on determining the cumulated activity in three contributing sources: 1) marrow; 2) blood; and 3) total body. The novel aspect of this method for estimating marrow radiation dose is derivation of the radiation dose for the entire red marrow from radiation dose estimates obtained by detection of cumulated activity in three lumbar vertebrae using a gamma camera. Contributions to the marrow radiation dose from marrow, blood, and total body cumulated activity were determined for patients who received an I-131 labeled MoAb, Lym-1, that reacts with malignant B-lymphocytes of chronic lymphocytic leukemia and nonHodgkin's lymphoma. Six patients were selected for illustrative purposes because their vertebrae were readily visualized on lumbar images. The radiation doses to the marrow contributed by nonpenetrating emissions in the marrow blood and penetrating emissions in the total body were similar in these patients with a mean of 0.2 and 0.3 rads per administered mCi from the blood and total body, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanism of contraceptive effect of low progestin doses

The effect of megestrol-acetate and ethynodiol-triacetate on the ovulation and on the division of impregnated ovules was examined. Experiments were performed on human oocysts. The progestins were also administered to animals with normal cycle. Males were placed with the females after 3 days of treatment. The time of fecundation was determined from the presence of spermatozoa in vaginal smears. The experiments with incubation of human ovules with megestrol-acetate or ethynodiol-diacetate indicated that maturation, fecundation and development of the ovules up to 4-8 blastomeres are not hindered. This was confirmed by the data obtained from a control group. Thus no cytotoxic effect of progestin was recorded in the preovulation period of the maturation nor during fecundation. The experiments with animals revealed no change in the character of the ovulation provoked by a 14-day treatment with progestins. These results allow to conclude that the contraceptive effect of megestrol-acetate and ethynodiol-diacetate is not linked with a damaging effect on the division of the ovule during its presence in the tubes.     

Comparative dynamics of elimination of potential chromosome damage in mouse bone marrow cells after low and moderate doses of radiation

Possible dynamics of the incidence, repair, and realization of potential chromosome aberrations (PAs) was examined by indirect methods based on cytogenetic analysis of radiation effects. PAs were characterized as chemical modifications of DNA responsible for the incidence of structural aberrations of chromosomes. We interpreted our data as providing evidence that two types of radiation-induced PAs, differing in repair rates, could occur in the exposed cells: quick- (short-term) and slow (long-term) repairing PAs. We showed that the PA spectrum gradually changed with an increase in radiation dose within the interval from 24 to 150 cGy. This process was paralleled by changes in the cell response and chromosome resistance to radiation. Short-term PAs were induced mainly by low radiation doses ranging from 24 to 75 cGy. Their incidence was associated with activation of the corresponding repair process. Further increase in radiation dose resulted in changes in the PA spectrum, and doses of 150 cGy induced predominantly long-term PAs with concomitant activation of the appropriate repair process. Induction of repair occurred in the dose intervals limited by lower and upper threshold doses, Dl and Du. In our experiments, short-term PAs were repaired when Dl < 24 cGy and 126 cGy < Du < < 150 cGy. Long-term PAs were repaired when 75 cGy < Dl < 99 cGy and Du > 150 cGy.     

Change in activity of microsomal cytochrome P-450-dependent monooxygenases from rat liver exposed to chronic low doses of radiation

The activity changes of cytochrome P-450-dependent monooxygenases of hepatic microsomal fraction were studied in, experimental animals after prolonged application (1 month) of low radiation doses (0.258 mkl/kg). The obtained results show the increase in catalytic activities of main forms of cytochrome P-450, participating in steroid hydroxylation, as well as the decrease in total content of cytochrome P-450 in hepatic microsomal fraction and the lowering of its demethylase activity.     

The relationship between radiation doses and their effects

Dose-effect relationships have been developed both for the biological effects studied by Radiobiology and the long-term pathological effects (malignant diseases) studied by Radiation Protection. The former approach chiefly considers the primary biological injuries at the cellular level, and the relationship between the dependent variable characteristic of the effect and the dose--an independent variable--has an explanatory meaning. The parameters associated to the independent variable have a biophysical signification and fit into a model of the action of ionizing radiations. In the latter approach, the relationship is pragmatic and the previous parameters are just the result of a curve-fitting procedure realized on experimental or human data. The biophysical models have led to a general formulation associating a linear term to a quadratic term both of them weighted by an exponential term describing cellular killing at the highest doses. To a certain extent the curves obtained for leukemias, bronchopulmonary and breast cancers prove the validity of the pragmatic model.