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Emergency localization of radioactive seeds lost during intracoronary brachytherapy.

Recently, it has been reported that brachytherapy catheters ruptured in vivo. Localization of lost beta-radiation-emitting seeds is a problem because no appropriate technique is available that is rapid and precise. We developed a technique to localize beta-emitting seeds utilizing the effect that beta-radiation induces bremsstrahlung. The loss of a single radioactive source was simulated in an Alderson Phantom representing a human body. The beta-induced bremsstrahlung could be detected selectively by a gamma-camera. The position of the radioactive seed could be located within 5 min with an accuracy of +/- 0.5 cm. The result of this study suggests that in an emergency case of loss of a brachytherapy source, a commercially available gamma-camera can be a valuable tool to detect lost beta-radiation-emitting seeds rapidly and precisely. In addition, the technique minimizes the patient's as well as the surgeon's exposure to radiation and reduces the extent of surgical trauma.

Beta Particles↗

Real-world clinical practice of intracoronary radiation therapy as compared to investigational trials.

Intracoronary radiation therapy (IRT) is well established in clinical practice as an effective treatment for in-stent restenosis. We aimed to determine if the 6-month clinical outcome of patients treated postapproval for marketing [commercial radiation (CR)] is equivalent to those patients enrolled in the Washington Radiation for In-Stent Restenosis Trials [Gamma WRIST and Beta WRIST; investigational radiation (IR)]. The 6-month clinical outcome of 110 consecutive patients with 125 lesions who received IRT (gamma, (192)Ir, 15-18 Gy, n = 6; or beta, (32)P, 20 Gy, n = 20; or (90)Sr/Y, 18.4-23.0 Gy, n = 99) in CR was compared with the 6-month clinical outcome of 117 patients with 117 lesions who received IRT ((192)Ir, 15 Gy, n = 65, in Gamma WRIST; and (90)Y, 20.6 Gy, n = 52, in Beta WRIST) in IR. Patients in CR were treated with wider radiation margins. The CR received antiplatelet therapy for at least 6 months and the IR for 1 month. The baseline characteristics of both groups were similar. Use of atheroablation devices was less in CR than IR (15.2% vs. 32.8%, respectively; P = 0.001). The overall major adverse cardiac events (death, Q-wave myocardial infarction, and target vessel revascularization; 18.2% vs. 29.1% in IR; P = 0.05) were significantly lower in the CR when compared with patients in the IR. The real-world clinical practice of IRT demonstrates lower events and better clinical outcomes. This is most likely a result of implementation of the lessons learned from the clinical trials such as optimizing the dosimetry by using a higher dose, treating wider margins to minimize edge effect, and administering prolonged antiplatelet therapy to abolish late thrombosis.

Aged↗

Long-term clinical and angiographic outcome of patients with occlusive in-stent restenosis treated with (32P) beta-brachytherapy.

The objective of this study was to determine the safety and efficacy of (32)P beta-brachytherapy in totally occlusive in-stent restenosis (ISR). Patients with occlusive ISR were generally excluded from the randomized clinical trials on intracoronary brachytherapy (utilizing either gamma- or beta-sources) that have shown reductions in restenosis rate and need for revascularization procedures. We analyzed short- and long-term effects of (32)P beta-brachytherapy (20 Gy) in 27 patients (28 lesions) with occlusive ISR and 84 (99 lesions) patients with nonocclusive high-risk ISR. The primary outcome measure was frequency of in-lesion angiographic binary restenosis at 7 months. Secondary endpoints were rates of major adverse cardiac events (MACE), target vessel revascularization (TVR), clinically driven TVR, and target lesion revascularization (TLR). (32)P beta-brachytherapy was feasible and safe and provided similar postprocedural angiographic results in the two clinically comparable groups. However, the 7-month binary restenosis rate was higher in the occlusive group, as were the MACE and late total occlusion rates. Multivariate logistic analysis of the overall population indicated occlusive pattern to be the only independent predictor of angiographic restenosis. In both groups, recurrent lesions most often showed a focal pattern with significant reduction of length. Although safe and effective in high-risk ISR, (32)P brachytherapy at 20 Gy does not appear to be sufficient to avoid long-term restenosis in patients with occlusive lesions. Further studies should determine the most suitable source and dosage of brachytherapy for patients with occlusive ISR.

Aged↗

Angiographic and clinical outcomes at 8 months of cutting balloon angioplasty and beta-brachytherapy for native vessel in-stent restenosis (BETACUT): results from a stopped randomized controlled trial.

The objective of this study was to assess angiographic and clinical outcomes of cutting balloon (CB) angioplasty and concomitant Sr/Y-90 beta-brachytherapy as a treatment modality for patients with native vessel in-stent restenosis (ISR). Procedural advantages over the standard balloon (SB) have been claimed for the CB. Intracoronary brachytherapy preceded by SB angioplasty is regarded as the treatment of choice in patients with ISR. In an interim analysis of a prospective randomized trial designed for 652 patients, 100 consecutive patients with ISR were assigned to treatment with SB angioplasty (n = 51) or CB angioplasty (n = 49), followed in either case by Sr/Y-90 beta-brachytherapy. Quantitative coronary angiography at baseline, postintervention, and at 8 months was performed by an independent central laboratory. More than 90% of target lesions in the overall patient population were diffuse, with 14% of stents totally occluded. Procedural parameters and immediate angiographic outcomes were essentially the same in either study arm. At 8 months, no statistically significant differences were observed in recurrent angiographic restenosis (SB = 26.1%; CB = 29.5%; P = 0.82), target lesion revascularizations (SB = 13.7%; CB = 8.2%; P = 0.53), and major adverse cardiac events (SB = 15.7%; CB = 8.2%; P = 0.36). In this interim analysis, there was no indication of a beneficial effect of CB use over SB use in terms of angiographic or clinical outcomes at 8-month follow-up. CB angioplasty appears to be as safe and efficacious as SB angioplasty in beta-radiation treatment of patients with predominantly diffuse native vessel ISR. It was decided to discontinue the trial.

Aged↗

Three-year follow-up after intracoronary beta-radiation therapy for in-stent restenosis.

BACKGROUND: Most studies that proved intracoronary radiation therapy (IRT) to be highly effective to reduce recurrent restenosis after treatment of in-stent restenosis (ISR) have looked at time periods up to 12 months. Whether the beneficial effect from radiation is sustained during long-term follow-up remains a concern. This study sought to evaluate the effectiveness of IRT using a beta-emitter during a 3-year follow-up period. METHODS: One hundred twenty-eight consecutive symptomatic patients (mean age, 63 +/- 11 years) with 134 in-stent restenotic lesions were treated for ISR with IRT (noncentred beta-emitter, Novoste; radiation dosis 21.1 +/- 3.1 Gy). Six-month angiographic follow-up was obtained in 104 patients (81%) with 105 lesions (78%). All patients underwent 36-month clinical follow-up. RESULTS: Six-month angiographic restenosis rate was 22% in stent (29% in lesion) with an in-stent late loss of 0.49 +/- 0.62 mm. Target lesion resvascularization (TLR) at 6-month follow-up was performed in 23 cases (18%). MACE (death, myocardial infarction, and target vessel revascularisation) was observed in 24 patients (19%). At 36-month follow-up, TLR increased to 36 cases (28%) and MACE was observed in 47 patients (37%). In a multivariate analysis, minimal lumen diameter before treatment of ISR using IRT was the only predictor of recurrent TLR at 36 months (OR = 0.131; 95% CI, 0.068-0.254; p = 0.002). In a subgroup of patients (N = 15) without restenosis at 6-month angiography but with clinically driven recurrent late angiography (mean, 18 +/- 7 months); in-lesion late loss increased from 0.47 +/- 0.54 mm at 6 months to 1.27 +/- 0.76 mm at repeated angiography (p = 0.005). CONCLUSION: There is a considerable number of delayed recurrent restenosis post IRT for ISR. This is due to ongoing late loss more than 6-month post IRT. The minimal lumen diameter before IRT predicts the need for recurrent TLR at 36 months.

Aged↗

Prevention of coronary restenosis with radiation therapy: a review.

The problem of restenosis after percutaneous transluminal coronary angioplasty remains the major limiting factor of the procedure. Over the last 10 years, investigators have been studying the use of radiation therapy for preventing restenosis after angioplasty or stent placement. Since radiotherapy has been proven in other cases to be effective in disrupting the cell cycle regulatory proteins and thereby slowing or stopping growth, it was decided to apply the same principle to neointimal hyperplasia. To review the data that have emerged regarding vascular radiation with an emphasis on irradiated stents, 65 articles were reviewed and both preclinical and clinical experiments were included. Overall, studies with gamma and beta radiation show promising results. Endovascular gamma radiation has been shown effective in randomized trials, even at 3-year follow-up. Beta radiation is preferred because of greater safety and localization, and because it has also shown encouraging results in initial clinical trials, as well as in larger randomized studies. Consequently, the Federal Drug Administration has approved the use of both. In both types of endovascular brachytherapy, it seems the greater the dose, the better the initial response. Safety concerns include an increased incidence of late thrombosis and greater restenosis at margins. With irradiated stents, however, the situation is not as clear. At times, animal models have presented confusing results. These have ranged from significant suppression of hyperplasia to outright adverse effects of radiation on the vessel wall. While some clinical trials have been encouraging, others have not. Follow-up of up to 1 year has been disappointing so far. Many issues, such as the "candy wrapper" effect and rebound hyperplasia, must be dealt with before this becomes a viable form of therapy. It has become clear that radiation therapy in this setting, while having potentially great benefits, can cause deleterious effects as well. However, the mixed bag of positive and negative results seen so far, and the attractiveness of stents or percutaneous transluminal coronary angioplasty being "restenosis-proofed," eventually is cause for cautious optimism.

Angioplasty, Balloon, Coronary↗

Chemical durability of Y2O3-Al2O3-SiO2 glasses for the in vivo delivery of beta radiation.

Microspheres made from Y2O3-Al2O3-SiO2 (YAS) glasses, which contain radioactive Y-90, are currently being used to treat liver cancer in humans, where their chemical durability is of prime importance. In deionized water or saline at 37 degrees C, the weight percent Yttrium (Y) dissolved from eight different YAS glasses ranged from only 0.02-0.13% of the total Y present and their dissolution rate was barely measurable, < or = 1.0 x 10(-9) g/cm2-min. The most chemically durable YAS glass was 17Y2O3-19Al2O3-64SiO2, mol%. The small amount of Y released from microspheres, 25-35 microns diameter, of this glass after corrosion in saline or deionized water at 37 degrees C was essentially the same as for bulk glass samples. Based on their excellent chemical durability, it is concluded that YAS glass microspheres are suitable for in vivo use.

Aluminum Oxide↗

Human fibroblast reactions to standard and electropolished titanium and Ti-6Al-7Nb, and electropolished stainless steel.

Stainless steel (SS), titanium (cpTi), and Ti-6Al-7Nb (TAN) are frequently used metals in orthopedic internal fracture fixation. Although reactivity to SS and cpTi are noted in reference, the soft tissue compatibility of TAN has not been comprehensively studied. This study focuses on the in vitro soft tissue compatibility of TAN in comparison to SS and cpTi using a human fibroblast model. The industrial standard surface finishes of these three materials vary considerably in view of their use in similar applications. To distinguish between material parameters of topography and chemistry, we have included electropolished (e.p) counterparts of the standard preparations of cpTi and TAN in the study (standard SS is e.p). All materials were characterized using atomic force microscopy, profilometry, and scanning electron microscopy. Our findings demonstrate that cell morphology and growth rate was similar for SS, and e.p. cpTi and TAN, with cells well spread and forming a confluent monolayer by 10 days. Cell growth on standard cpTi was similar to the electropolished samples; however, they showed a less spread morphology with more filopodia and surface ruffling present. Cell morphology on standard TAN was rounded or elongated and proliferation was inhibited at all time points, with possible cell necrosis by day 10. We found evidence of endocytosis of beta-phase particles originating from the standard TAN surface. We believe that the particle uptake coupled with the characteristic surface topography contribute to the noncytocompatibility of fibroblasts on standard TAN.

Biocompatible Materials↗

Study of the influence of beta-radiation on the properties and mineralization of different starch-based biomaterials.

In this work, the effects of beta-radiation are assessed, for the first time, on starch-based biodegradable polymers, with the aim of using it as an alternative sterilization process to the previously studied sterilization methods. Different doses of radiation were used in order to investigate the possibility of using this sterilization technique as a treatment to tailor the surface and bulk properties (namely mechanical) of these polymers. The as-treated substrates were characterized by water-uptake measurements and contact angle (theta) measurements. The mechanical properties of the materials were characterized by tensile tests by means of ultimate tensile strength (UTS) and strain at break (epsilon). The fracture of the surfaces was observed by scanning electron microscopy (SEM). Dynamic mechanical analysis (DMA) was also used to characterize the viscolelastic behavior of the irradiated materials. The main effect of sterilization with beta-radiation over the starch-based polymers seems to be a surface modification by an increase of the hydrophilicity. Nevertheless, because beta-radiation did not significantly affect the mechanical properties, it can be regarded as an effective way of modifying the surface for applications were more hydrophilic surfaces are desirable.

Beta Particles↗

An efficient targeted radiotherapy/gene therapy strategy utilising human telomerase promoters and radioastatine and harnessing radiation-mediated bystander effects.

BACKGROUND: Targeted radiotherapy achieves malignant cell-specific concentration of radiation dosage by tumour-affinic molecules conjugated to radioactive atoms. Combining gene therapy with targeted radiotherapy is attractive because the associated cross-fire irradiation of the latter induces biological bystander effects upon neighbouring cells overcoming low gene transfer efficiency. METHODS: We sought to maximise the tumour specificity and efficacy of noradrenaline transporter (NAT) gene transfer combined with treatment using the radiopharmaceutical meta-[(131)I]iodobenzylguanidine ([(131)I]MIBG). Cell-kill was achieved by treatment with the beta-decay particle emitter [(131)I]MIBG or the alpha-particle emitter [(211)At]MABG. We utilised our novel transfected mosaic spheroid model (TMS) to determine whether this treatment strategy could result in sterilisation of spheroids containing only a small proportion of NAT-expressing cells. RESULTS: The concentrations of [(131)I]MIBG and [(211)At]MABG required to reduce to 0.1% the survival of clonogens derived from the TMS composed of 100% of NAT gene-transfected cells were 1.5 and 0.004 MBq/ml (RSV promoter), 8.5 and 0.0075 MBq/ml (hTR promoter), and 9.0 and 0.008 MBq/ml (hTERT promoter), respectively. The concentrations of radiopharmaceutical required to reduce to 0.1% the survival of clonogens derived from 5% RSV/NAT and 5% hTERT/NAT TMS were 14 and 23 MBq/ml, respectively, for treatment with [(131)I]MIBG and 0.018 and 0.028 MBq/ml, respectively, for treatment with [(211)At]MABG. CONCLUSIONS: These results indicate that the telomerase promoters have the capacity to drive the expression of the NAT. The potency of [(211)At]MABG is approximately three orders of magnitude greater than that of [(131)I]MIBG. Spheroids composed of only 5% of cells expressing NAT under the control of the RSV or hTERT promoter were sterilised by radiopharmaceutical treatment. This observation is indicative of bystander cell-kill.

Astatine↗

Frequent p53 mutation in mouse tumors induced by repeated beta-irradiation.

On examination of cDNA of the p53 gene in 65 murine tumors of the skin and bone produced by repeated exposure to a suprathreshold dose of 1-8 Gy of 90Sr-90Y beta-radiation per exposure, we found 20 cases of mutation: 11 minute deletions (loss of 1-24 bp), including two cases possibly due to aberrant splicing; three insertions of 4-8 bp; and six base-pair substitutions, including four at CpG sites, three being identical changes at codon 122 (a p53 hot spot). All but one of these mutations were confined to the central region of the p53 gene. From frameshifts created by deletions and insertions, the minimum size of the mutant p53 proteins found in these tumors was estimated to be 55% of the intact size. Cells of 17 of 19 tested tumors with p53 mutation were positive for immunostaining of p53 proteins accumulated in the nuclei and so were clearly different from nonneoplastic cells. Ha-ras mutation was absent in these tumors, indicating that repeated beta-irradiation created a cell-growth stimulating effect similar to that of ras mutation.

Animals↗

Mineral content changes in bone associated with damage induced by the electron beam.

Energy-dispersive x-ray (EDX) spectroscopy and backscattered electron (BSE) imaging are finding increased use for determining mineral content in microscopic regions of bone. Electron beam bombardment, however, can damage the tissue, leading to erroneous interpretations of mineral content. We performed elemental (EDX) and mineral content (BSE) analyses on bone tissue in order to quantify observable deleterious effects in the context of (1) prolonged scanning time, (2) scan versus point (spot) mode, (3) low versus high magnification, and (4) embedding in poly-methylmethacrylate (PMMA). Undemineralized cortical bone specimens from adult human femora were examined in three groups: 200x embedded, 200x unembedded, and 1000x embedded. Coupled BSE/EDX analyses were conducted five consecutive times, with no location analyzed more than five times. Variation in the relative proportions of calcium (Ca), phosphorous (P), and carbon (C) were measured using EDX spectroscopy, and mineral content variations were inferred from changes in mean gray levels ("atomic number contrast") in BSE images captured at 20 keV. In point mode at 200x, the embedded specimens exhibited a significant increase in Ca by the second measurement (7.2%, p < 0.05); in scan mode, a small and statistically nonsignificant increase (1.0%) was seen by the second measurement. Changes in P were similar, although the increases were less. The apparent increases in Ca and P likely result from decreases in C: -3.2% (p < 0.05) in point mode and -0.3% in scan mode by the second measurement. Analysis of unembedded specimens showed similar results. In contrast to embedded specimens at 200x, 1000x data showed significantly larger variations in the proportions of Ca, P, and C by the second or third measurement in scan and point mode. At both magnifications, BSE image gray level values increased (suggesting increased mineral content) by the second measurement, with increases up to 23% in point mode. These results show that mineral content measurements can be reliable when using coupled BSE/EDX analyses in PMMA-embedded bone if lower magnifications are used in scan mode and if prolonged exposure to the electron beam is avoided. When point mode is used to analyze minute regions, adjustments in accelerating voltages and probe current may be required to minimize damage.

Adult↗

Quantitative validation of an intracerebral beta-sensitive microprobe system to determine in vivo drug-induced receptor occupancy using [11C]raclopride in rats.

In this study, we evaluated the potential of using a new beta-sensitive microprobe system for in vivo quantification of [11C]raclopride binding and for in vivo determination of drug-induced receptor occupancy in the rat striatum. To validate this system, an ex vivo tissue dissection method was used to corroborate in vivo beta-microprobe measurements. Our data showed that the beta-microprobe-derived [11C]raclopride binding kinetics in striatum could be quantified using a tissue compartmental model with a cerebellar reference region. Haloperidol (0.001-0.1 mg/kg; i.v.) induced a dose-dependent decrease in [11C]raclopride binding in striatum as measured using the beta-microprobe with an ED50 value of 0.013 mg/kg. Highly significant relationships (P < 0.0001) were observed, within the same animals, between in vivo and ex vivo measures of haloperidol-induced D2-receptor occupancy (r = 0.98) as well as between in vivo and ex vivo measures of [11C]raclopride binding potentials (r = 0.99). Results from pretreatment and displacement studies with unlabeled raclopride and amphetamine conformed to the effect of these drugs as observed in humans using [11C]raclopride and PET and allowed estimation of the in vivo k(off) value of raclopride to 0.025 +/- 0.004 min(-1). However, allowing the system to stabilize before measurements and shielding the photomultiplier tubes were critical for obtaining these consistent results. This study demonstrates that the beta-microprobe provides reliable measurements of [11C]raclopride binding kinetics in rodents, allows for quantitative in vivo measurements of antipsychotic drug action in brain, and represents a valid and cost-effective alternative to positron emission tomography imaging in small animals.

Animals↗

Proposition for assessment of quantitative whole-body autoradiography.

To assess recent improvements in quantitative whole-body autoradioluminography (QWBA), the entire QWBA procedure was divided into five processes. Each process was then investigated carefully to determine whether there were any problems in defining a clear standard operating procedure. Results show that use of two instruments, Macro-Cut, Leica, Germany, and the Bioimaging Analyzer with IP, Fuji Photo Film, was essential to produce macroautoradiographs for QWBA data. The remaining problems include the process for freezing the animal carcass and the process for freeze-drying or lyophilizing the frozen sections of the biomaterials. In addition, a desirable standard operating procedure (SOP) must be developed for assessing QWBA. This article proposes satisfactory SOPs with sufficient clarification and experimental proofs to ensure regulatory compliance for the QWBA technique.

Animals↗

18F-labeled fluorodeoxyglucose positron emission tomography-guided surgery for recurrent colorectal cancer: a feasibility study.

OBJECTIVE: Positron emission tomography (PET) scanning is an accepted diagnostic tool for the detection of colorectal cancer (CRC). The purpose of this study was to determine whether diagnostic information offered by preoperative PET scan could be used to detect disease intraoperatively using beta and gamma handheld probes. METHODS: Two studies were carried out. First, tumor "phantoms" were created using 62 microCi fluorodeoxyglucose (FDG) in a saline-filled basin. Gamma and beta handheld probes were used to determine detection characteristics with respect to probe type, distance from source, and isotope half-life. In a second study, probes were used intraoperatively to detect tumor in 10 patients with recurrent colorectal cancer as determined by preoperative PET scan. Counts relative to background were determined for each probe as was histopathologic correlation with probe-positive tissue. RESULTS: Phantom studies documented that FDG detection by each probe was nonlinearly related to source proximity and half-life. In human subjects, abnormal findings on preoperative PET studies were detected by both probes with tumor:normal ratios of 1.6 (beta) and 1.5 (gamma). All probe-positive tissue was histologically confirmed to be recurrent colorectal cancer. CONCLUSIONS: Intraoperative detection of CRC using an FDG source and beta and gamma probes correlates with preoperative PET. With further improvements in probe technology, successful differentiation of normal and tumor tissue as shown here may allow for more precise localization and directed resection.

Beta Particles↗

Rabbits as a model for the study of hyperlipoproteinemia and atherosclerosis.

Lipoproteins of normal and cholesteremic plasma were compared in New Zealand White (hyperresponder) and Dutch Belt (hyporesponder) rabbits. Three major differences were observed between the strains: (1) New Zealand White rabbits developed much higher plasma levels of very low, intermediate, and low density lipoproteins after cholesterol feeding; (2) Dutch Belt rabbits, normal and cholesteremic, had higher ratios of the more dense high density lipoproteins HDL3 (d 1.125-1.20 g/ml) to the less dense HDL2 (d 1.081-1.125 g/ml); (3) cholesteremic Dutch Belt rabbits had higher plasma levels of the more dense HDL3 subfraction than did cholesteremic New Zealand White rabbits. Cholesteremic very low density lipoproteins of both strains are large particles of beta electrophoretic mobility that are rich in cholesteryl esters and an arginine-rich apolipoprotein(s). The intermediate and low density lipoprotein fractions were similarly altered in composition, although the proportion of arginine-rich protein to total protein was ledd than in the very low density fraction. Although the high density lipoproteins were greatly decreased in concentration in cholesteremic plasma, no major changes in their apolipoproteins were seen in either strain of rabbits. The major high density apolipoprotein of rabbits occurs in two electrophoretically separable forms and is similar to human apo A-I. Six minor apolipoproteins were isolated from the high density lipoproteins; some of these occur also in other density fractions.

Adenosine Triphosphatases↗

Sister chromatid induction by beta-irradiation from incorporated 3H-thymidine: a paradox explained.

Sister chromatid exchanges (SCE's) induced by [3H]thymidine (3HdT) of increasing specific activities incorporated over one cycle and 5-bromodeoxyuridine (BrdUrd) over the two following cycles were investigated in synchronised Chinese hamster ovary (CHO) cells. SCEs induced during the first cycle on a T.T template (SCE 1) show little increase with dose compared with those induced in the second cycle on a 3HT.T template (SCE 2) where the linear increase with dose reflects that seen after X irradiation. During the third cycle, SCEs 3.1 and 3.2 are induced on unlabelled T.B or labelled 3HT.B templates respectively. These templates are theoretically present in a 1:1 ratio after random segregation at second metaphase. Over practically the entire dose range however, the ratio 3.1/3.2, which decreased with dose, was greater than 1.0 and similar to the high values obtained by other workers. At increasing times after BrdUrd introduction, the ratio decreased from greater than 1.0 to less than 1.0. Measurements showed that the expected 50% level of labelled chromosomes at metaphase in the samples could vary between 42%-59%. Cells with greater than 50% labelled chromosomes were more delayed in the cell cycle due to the 3H-irradiation than those with less than 50%. Early fixations therefore favoured SCE 3.1 while late favoured SCE 3.2. SCEs due to BrdUrd in 3HT.B and T.B templates showed no synergistic interaction with irradiation-induced SCEs. When these BrdUrd-induced SCEs were removed from the totals then the 3H-induced SCE levels in 3HT.T, and 3HT.B templates (SCE 2 and 3.2) were similar and increased at a similar rate with dose. This was 2-3 times faster than in SCE 1 and 3.1 where the SCE levels due to irradiation were again similar but lower than for 2 and 3.2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗