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Biomedical subjects

R K Jeevanram

Publications and source records attributed to R K Jeevanram.

At least 19 recordsLinked to original sources

Dose-rate effect on the induction of HPRT mutants in human G0 lymphocytes exposed in vitro to gamma radiation.

The influence of dose rate on expression time, cell survival and mutant frequency at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus was evaluated in human G(0) peripheral blood lymphocytes exposed in vitro to gamma rays at low (0.0014 Gy/min) and high (0.85 Gy/min) dose rates. A cloning assay performed on different days of postirradiation incubation indicated an 8-day maximum expression period for the induction of HPRT mutants at both high and low dose rates. Cell survival increased markedly with decreasing dose rate, yielding D(0) values of 3.04 Gy and 1.3 Gy at low and high dose rates, respectively. The D(0) of 3.04 Gy obtained at low dose rate could be attributed to the repair of sublethal DNA damage taking place during prolonged exposure to low-LET radiation. Regression analysis of the mutant frequency yielded slopes of 12.35 x 10(-6) and 3.66 x 10(-6) mutants per gray at high and low dose rate, respectively. A dose and dose-rate effectiveness factor of 3.4 indicated a marked dose-rate effect on the induced HPRT mutant frequency. The results indicate that information obtained from in vitro measurements of dose-rate effects in human G(0) lymphocytes may be a useful parameter for risk estimation in radiation protection.

Cells, Cultured↗

Studies on the HPRT mutant frequency in T lymphocytes from healthy Indian male population as a function of age and smoking.

Mutant frequency at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene in the peripheral blood lymphocytes obtained from 44 healthy individuals (23 non-smokers and 21 smokers) of an Indian male population was studied using T-lymphocyte cloning assay. It was found that lnMF increased with age at a rate of 2.5% per year (P <0.001). Blood samples from smokers showed a significant (P <0.037) increase in HPRT mutant frequency (MF) (10.43 +/- 4.74 x 10(-6)) as compared to that obtained from non-smokers (7.69 +/- 3.69 x 10(-6)). This study also showed a significant (P <0.027) inverse correlation between lnMF and non-selected cloning efficiency (CE). However, with respect to age no variation was observed in cloning efficiency. The results obtained in this study showed a good comparison with those reported in different populations of the world.

Adult↗

Comparison of inter- and intra-chromosomal aberrations in blood samples exposed to different dose rates of gamma radiation.

Peripheral blood samples obtained from a normal healthy volunteer were exposed in vitro to gamma radiation with various doses at different dose rates of 1.0, 0.1 and 0.0014 Gy min(-1). The exposed samples were analysed for different chromosomal aberrations such as dicentrics (DC), centric rings (CR) and double-minutes (DM). The ratio of DC chromosomes (inter) to the total number of centric rings (CR) and double-minutes (DM) (CR + DM = intra) were analysed for all the three dose rates. The study showed that the frequency of inter-arm chromosomal aberrations was more then three times higher than that observed with intra-arm chromosomal aberrations in samples exposed at a dose rate of 1.0 and 0.1 Gy min (-1). However, the frequency of inter- and intra-arm chromosomal aberrations were almost same (ratio 1:1) in samples exposed at a dose rate of 0.0014 Gy min(-1). This paper discusses the usefulness of the ratio of inter- and intra-arm chromosome aberration in finding out whether the sample was exposed to high or low dose rate radiation.

Adult↗

DNA damage and integrity of UV-induced DNA repair in lymphocytes of smokers analysed by the comet assay.

DNA damage was assessed in smoker lymphocytes by subjecting them to the single cell gel electrophoresis (SCGE) assay. In addition to the appearance of comet tails, smoker cells exhibited enlarged nuclei when analysed by the comet assay. On comparing basal DNA damage among smokers and a non-smoking control group, smoker lymphocytes showed higher basal DNA damage (smokers, 36.25+/-8.45 microm; non-smokers, 21.6+/-2.06 microm). A significant difference in DNA migration lengths was observed between the two groups at 10 min after UV exposure (smokers, 65.5+/-20.34 microm; non-smokers, 79.2+/-11.59 microm), but no significant differences were seen at 30 min after UV exposure (smokers, 21.13+/-10.73 microm; non-smokers, (27.2+/-4.13 microm). The study thus implies that cigarette smoking perhaps interferes with the incision steps of the nucleotide excision repair (NER) process. There appeared be no correlation between the frequency of smoking and DNA damage or the capacity of the cells to repair UV-induced DNA damage that suggests inherited host factors may be responsible for the inter-individual differences in DNA repair capacities. The study also suggests monitoring NER following UV insult using the SCGE assay is a sensitive and simple method to assess DNA damage and integrity of DNA repair in human cells exposed to chemical mutagens.

Adult↗

Environmental radiation as the conditioning factor for the survival of yeast Saccharomyces cerevisiae.

Whether natural radiation can be a conditioning factor for the growth and survival of a living organism was investigated using diploid yeast S. cerevisiae D7. Yeast cells were conditioned by growing them continuously for at least 100 generation in 3 different radiation background such as i) ambient radiation (1.1 mSv/y), ii) sub-ambient radiation (0.44 mSv/y, within a shielded chamber) and iii) an elevated background radiation (88 and 880 mSv/y in a gamma-field). At the end, the cells were challenged with 60Co gamma, 100 Gy and the viable fractions were determined. Conditioning the cells in 880 mSv/y and in ambient radiation, enabled the cells to reduce the deleterious effect of the challenging dose significantly (P < 0.05) compared to that of sub-ambient radiation. The cellular viability of yeast cultures seems to be influenced by the prevailing radiation background, apart from starvation. Comparatively, a rapid decline in viability was noticed when the cultures were incubated for 60 days in the shielded chamber. The results indicate that some amount of radiation equivalent to background level or little above is needed to confer fitness in biological systems against stress factors, including radiation. The adaptive dose for the diploid yeast was also determined by single exposure. The priming dose ranged from 0.01 to 1.2 Gy. An adaptive dose of 0.25 or 0.4 Gy, almost nullified the deleterious effect of the challenging dose. The adaptive response may have a greater role in the field of cancer therapy and in radiation risk assessment. Understanding the response of an organism at different radiation-background will be helpful for successful space management.

Adaptation, Physiological↗

Comparison of chronic exposures received by radiation workers using different biological end-points with the doses recorded by TLD.

The frequency of different biological end-points such as translocation, dicentrics (DC) and micronuclei (MN) was studied in 14 radiation workers and 21 non-radiation workers. The average frequencies for different types of aberrations were significantly higher in radiation workers compared to those of respective aberrations in non-radiation workers. Out of 14 radiation workers, eight subjects showed a dose above the detection limit as per translocation and seven subjects as per DC frequency and no patient showed a dose above the detection limit as per MN frequency. Regression analysis carried out between the recorded doses according to Thermo Luminescence Dosimeter (TLD) and the dose estimated as per translocation frequency gave a correlation coefficient of 0.32, whereas that obtained with TLD dose and the dose estimated as per DC was 0.81. When the correlation was made between the TLD dose, which was above 0.15 Gy (the detection limit for translocation), and the dose estimated as per translocation frequency in these subjects, a correlation coefficient of 0.98 was found. A similar analysis between the TLD dose above 0.5 Gy (the detection limit for DC) and the dose estimated as per DC frequency in these subjects, a correlation coefficient of 0.26 resulted. This paper discusses the reasons for the poor correlation obtained between TLD dose and dose estimated as per DC and MN frequency.

Adult↗

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,.

Adult↗

Estimation of dose in cancer patients treated with fractionated radiotherapy using translocation, dicentrics and micronuclei frequency in peripheral blood lymphocytes.

The frequency of translocation, dicentrics (DC) and micronuclei (MN) was studied in blood samples exposed in vitro to (60)Co gamma radiation and cervical cancer patients undergoing fractionated radiotherapy. The samples exposed under in vitro condition showed that the frequency of translocation and dicentric followed Poisson distribution ('u' varied between -0.04 and +1.41 for translocation and between -0.09 and +1.81 for DC) and that obtained with MN follow over dispersion ('u' varied between +2.04 and +9.28). However, the cervical cancer patients undergoing radiotherapy showed over dispersion for all these three aberrations (DC, MN and translocation). The frequencies of aberrations obtained in cancer patients were found to be lower than those obtained for in vitro exposure for doses more than 2 Gy equivalent whole body dose (EWBD). The dose-response curves were constructed using the frequencies of DC, MN and translocation as a function of EWBD. Doses as measured from the dose response curves were compared with the estimated dose in order to check whether the measured and estimated doses agree. The percent variation between the doses measured from aberration frequencies and that of the estimated dose was lower with translocation (10.8+/-7.41%) compared to those obtained with DC (38. 08+/-31.85%) and MN (47.19+/-31.80%).

Adolescent↗

Higher frequency of dicentrics and micronuclei in peripheral blood lymphocytes of cancer patients.

The presence of dicentric chromosome (DC) and micronuclei (MN) frequency in the peripheral blood lymphocytes of 25 cancer patients prior to chemo and radiotherapy and 21 healthy volunteers were studied. The overall DC and MN showed significantly higher frequency compared to those obtained in normal healthy volunteers (p<0.0001). However, among 25 patients only 15 showed a higher frequency of DC aberration, nine patients showed the presence of minutes (M) and seven patients showed chromatid breaks (ChB). The reasons for the higher frequency of aberration observed in these cancer patients are discussed in this paper.

Adult↗

Influence of in vitro low-level gamma-radiation on the UV-induced DNA repair capacity of human lymphocytes--analysed by unscheduled DNA synthesis (UDS) and comet assay.

Unscheduled DNA synthesis (UDS) induced by ultraviolet radiation (UV) was studied in human lymphocytes after exposing blood samples in vitro to doses ranging between 1 and 10 mGy gamma-radiation, by way of measuring tritiated thymidine (3H-TdR) uptake in the DNA of these lymphocytes. The results indicate that samples pre-exposed to gamma-ray doses ranging between 2.5 and 4 mGy show higher UDS levels compared with those pre-exposed to doses of less than 2.5 or more than 4 mGy. These results were verified by studying the rate of removal of UV-induced photoproducts using the comet assay. The reason for the increase in DNA repair capacity in this dose range is discussed in comparison with earlier reports on this phenomenon. The DNA repair capacity with respect to inter-individual variability and age is also analysed. The study implies that the comet assay is a simple and sensitive visual method to track nucleotide excision repair and hence can be used to estimate UV-induced DNA repair in the place of the more reliable yet cumbersome and time-consuming, grain-counting autoradiographic technique.

Adult↗

A comparative study of synchronised and conventional culture methods on the micronucleus dose-response curve.

Micronucleus (MN) dose-response curves have been studied in blood samples obtained from a healthy volunteer with both a methotrexate synchronised culture and with a conventional culture method. The curve obtained with the synchronised culture, showed better response at higher doses compared to that obtained with the conventional procedure. Generally, MN frequency obtained at a dose of 4.0 Gy with the conventional procedure is lower, compared to that obtained with dicentric (DC) frequency. The present study also showed that MN frequency obtained at this dose was lower (0.79 +/- 0.09) compared to that obtained with DC frequency (0.91 +/- 0.10). However, DC frequency obtained with the synchronised culture was almost the same as that obtained with the conventional method, whereas acentric frequency showed an increase with the synchronised culture. The study showed that the ratios of MN frequency/total aberration frequency observed with the synchronised (0.63) and that obtained with the conventional culture (0.59) was more or less the same indicating that higher acentric frequency may be the cause for higher MN frequency in the synchronised culture. The present study indicates that methotrexate may not be the cause of higher acentric frequency in synchronised culture. A possible reason for the higher acentric frequency in the synchronised culture, is highlighted.

Cell Culture Techniques↗

Analysis of radiation dose-response curve obtained with cytokinesis block micronucleus assay.

The frequency of micronuclei and acentrics obtained with different doses of 60Co gamma radiation was examined. When compared to acentric frequency the micronuclei frequency was found to be higher at about 115% for doses below 1 Gy. However, it dropped to about 65% as the dose was increased to 4 Gy. This paper discusses the causes for the reduced frequency of micronuclei at higher doses by taking into account the possibility of their being masked from view by the daughter nuclei in the binucleated cell.

Dose-Response Relationship, Radiation↗

A simple non-distillation method for the estimation of Ru-106 in urine.

A simple method has been developed for estimating Ru-106 in urine. Urine samples spiked with 3-50 Bq of Ru-106 and 200 micrograms of ruthenium carrier were initially oxidized using an HNO3-H2O2 mixture. Attempts to recover ruthenium by various preconcentration methods after the initial oxidation resulted in recoveries ranging from 10-54% depending on the experimental conditions. For near quantitative recoveries, the organic matter in urine was completely destroyed by wet ashing with HNO3-H2O2 (method A) or HNO3-H2O2 followed by H2SO4 treatment (method B). The ruthenium was oxidized to RuO4 using potassium periodate and allowed to react in situ with polyethylene powder. The polyethylene powder was separated, washed and its beta activity was counted. The recovery of ruthenium was 86.9 +/- 4.6% (RSD 5.3%) in method A; and 94.4 +/- 2.6% (RSD 2.8%) in method B. The minimum detection limit achieved was 0.59 Bq/dm3. Interferences due to Cs-137 and Sr-90 were studied.

Humans↗

Simultaneous spectrophotometric estimation of thorium and calcium in urine.

A simple and rapid method for the simultaneous estimation of thorium and calcium in urine was developed. Thorium and calcium were coprecipitated as oxalates at pH 3-4 and were determined using Thoronol as reagent. A multi-wave-length linear regression analysis procedure was applied. Thorium recovery was found to be 78.3% +/- 5.1% (1 sigma) and that of calcium was 93.7 +/- 3.0% (1 sigma). The minimum detection limit for thorium was found to be 2.54 mBq/dm3. The analytical results of calcium agree very well with those determined by EDTA titrimetry.

Calcium↗

Thyroid abnormalities in the McCune-Albright syndrome: ultrasonography and hormonal studies.

Hyperthyroidism and goiter have been reported frequently in association with the McCune-Albright syndrome (MAS). To assess the prevalence and extent of thyroid abnormalities in girls with MAS, we studied 19 patients [mean age, 6.6 +/- 1 (+/- SE) yr; mean bone age, 9.5 +/- 1 yr] and 18 normal control girls (mean age, 10.3 +/- 0.5 yr). All patients appeared euthyroid when examined; 1 was taking antithyroid medication. Ultrasonography revealed thyroid abnormalities in 7 patients, including generalized inhomogeneity, small (2-4 mm) and large (greater than 10 mm) hypoechoic regions, and echogenic nodule-like regions. Repeat ultrasonography after intervals of 9-18 months showed enlargement of large hypoechoic regions in 2 patients. In the patients with abnormal ultrasound findings, serum TSH was uniformly low or suppressed both at baseline and after administration of 7 micrograms/kg TRH. The mean serum T3 level in this group was significantly higher than that in controls (2.9 +/- 0.2 vs. 2.3 +/- 0.1 nmol/L; P less than 0.05), whereas mean serum T4, free T4, and T4-binding globulin levels did not differ from those of controls. In the remaining 11 patients, thyroid ultrasonography was normal, and the serum levels of T3, T4, free T4, and TSH were normal. Bioassay showed no detectable thyroid-stimulating activity in the plasma of the MAS patients with suppressed TSH levels. None of the patients became overtly thyrotoxic over 3-6 yr of observation, and their serum iodothyronine levels remained stable. We conclude that thyroid dysfunction is common in girls with MAS, but that it may be clinically occult and not rapidly progressive. The thyroid dysfunction, like that of the ovaries, is associated with structural abnormalities in the gland itself, together with suppressed levels of the respective stimulating hormones.

Adolescent↗

Influence of initial large dose on subsequent uptake of therapeutic radioiodine in thyroid cancer patients.

Fifty-two patients with differentiated thyroid cancer, following thyroidectomy were studied by administering a quantity of up to 5 mCi of [131I]sodium iodide. In most of these patients, radioiodine uptake values obtained with the subsequent therapeutic dose were markedly lower than those observed with the initial doses. This observation was verified in seven of the patients with differentiated thyroid cancer, by measuring the radioiodine uptake with a second dose of 4.5 mCi of [131I]sodium iodide. Calculations showed that the major etiology was probably therapeutic irradiation of the thyroid by the first dose.

Combined Modality Therapy↗

Synthesis of thyroglobulin in thyroid carcinoma patients after radioiodine therapy.

Endogenously radioiodinated thyroglobulin (Tg) and the serum concentration of Tg have been measured in patients with metastatic thyroid carcinoma after therapeutic doses of radioiodine. Serial samples of blood were analyzed for both these parameters over a period of 10 to 22 days. The specific activity of Tg (cpm/ng) was calculated for each sample. Among the six patients studied, three showed constant specific activity. The specific activity of the other three fell, indicating the entering of newly synthesized Tg into the circulation. The respective amounts of Tg entering into the circulation in these three patients were 120, 852, and 20,935 ng/ml serum/day.

Carcinoma↗

Immunoreactive thyroglobulin-like material derived from saliva.

The presence of an immunoreactive thyroglobulin-like material in saliva from normal subjects and from 35 patients with thyroid carcinoma was detected by radioimmunoassay. The levels of this material in saliva were markedly elevated in patients with extensive metastases. Concentrated saliva samples from normal subjects and from patients with thyroid carcinoma were fractioned on Sepharose-6B and each fraction was assayed from thyroglobulin content by RIA. Several protein peaks of varying molecular size with thyroglublin-like immunoreactivity were observed. The physiological significance of these molecules in saliva remains to be established.

Antibodies↗