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Paclitaxel restores radiation-induced apoptosis in a bcl-2-expressing, radiation-resistant lymphoma cell line.

PURPOSE: To restore radiation-induced apoptosis in a bcl-2-expressing, radiation-resistant murine lymphoma cell line (LY-ar) by pretreatment with paclitaxel (Taxol). Because this cell line also has high intracellular levels of glutathione (GSH), reportedly due to the bcl-2 expression and involved in the cell's antioxidant functions, paclitaxel treatment was correlated with GSH levels. METHODS AND MATERIALS: LY-ar cells were pretreated with paclitaxel and then irradiated with 5 Gy. Apoptosis was measured by DNA fragmentation 6 h later. Dose response and time course experiments were performed. Intracellular GSH levels were measured after treatment. Cell survival analysis was performed for various paclitaxel concentrations +/- 5 Gy. RESULTS: LY-ar cells pretreated with 0 nM, 10 nM, 25 nM, and 50 nM paclitaxel for 20 h underwent apoptosis at 2%, 15%, 25%, and 22%, respectively. With the addition of 5-Gy irradiation, LY-ar cell apoptosis increased to 4%, 30%, 49%, and 57%. Maximal apoptosis was detected with a paclitaxel pretreatment time of 20 h. Intracellular GSH levels were reduced by nearly 50% with paclitaxel pretreatment. Surviving fractions (SFs) with 0 nM, 10 nM, 25 nM, and 50 nM paclitaxel and 0 Gy were 1.0, 0.50, 0.08, and 0.05, respectively. SFs with 0 nM, 10 nM, 25 nM, and 50 nM paclitaxel and 5 Gy were 0.009, 0.003, 3 x 10(-5), and 1 x 10(-5), respectively. CONCLUSION: Radiation-induced apoptosis in LY-ar cells was restored by pretreatment with paclitaxel. This correlated with lowered levels of intracellular GSH. Cell survival analysis indicated that the combination of Taxol and radiation on cell killing was greater than additive.

Animals↗

Susceptibility to radiation-induced leukaemia/lymphoma is genetically separable from sensitivity to radiation-induced genomic instability.

PURPOSE: To determine whether there is a relationship between the genetics underlying the susceptibility to radiation-induced leukaemia in CBA/H (acute myeloid leukaemia, AML) and C57BL/6 (thymic lymphoma, TL) mice, and the genetics underlying the sensitivity of CBA/H (sensitive) and C57BL/6 (resistant) mice to radiation-induced chromosomal instability. MATERIALS AND METHODS: CBA/H, (CBA/H x C57BL/6)F1, F1 x CBA/H, F1 x C57BL/6 and F1 x F1 mice were exposed to a single acute dose of 3.0 Gy X-rays. AML and TL were diagnosed over the subsequent 30 months. RESULTS: There was no statistically significant difference in the incidence of AML in F1, F1 x F1, F1 x CBA/H and F1 x C57BL/6 mice, which was approximately 50% that in CBA/H mice. AML susceptibility is therefore a dominant polygenic trait, and both susceptibility and resistance (variable penetrance) CBA/H and C57BL/6 loci are involved. The incidence of TL in the FM and F1 x CBA/H mice was negligible, indicating that TL susceptibility is a recessive trait. As the TL incidence in the F1 x C57BL/6 mice was about half that in C57BL/6 mice, one recessive locus is probably involved. CONCLUSIONS: AML susceptibility in CBA/H mice is a dominant trait in contrast to the recessive inheritance of CBA/H sensitivity to radiation-induced chromosomal instability. TL-susceptibility in C57BL/6 is a recessive trait in contrast to the dominant inheritance of C57BL/6 resistance to radiation-induced chromosomal instability.

Animals↗

Multiple small exposures of filtered mid-UV radiation increase the resistance of Chinese hamster cells to far-UV, mid-UV and filtered mid-UV radiation.

The response of Chinese hamster cells (V79-MI2G) to multiple, low doses of filtered mid-UV radiation (wavelengths longer than 300 nm) were examined over an exposure period of 30 days. Cell survival and the induction of mutation at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus using resistance to 6-thioguanine (TG) were the endpoints in this study. With increasing total accumulated dose given at 500 J/m2/day as a single short exposure, an increased resistance to cell killing was observed. This increase in resistance to cell killing was accompanied by a gradual decrease in sensitivity to the induction of mutants resistant to 6-TG. Above total accumulated doses of 5000 J/m2 the frequency of 6-TG resistance did not increase. After multiple doses of filtered mid-UV radiation the cells became more resistant to subsequent challenges with acute doses of far-UV, mid-UV or filtered mid-UV. The increased resistance to the cell killing action and to the mutation induction by UV suggests that during exposure to low, multiple doses of filtered mid-UV radiation the cells become adapted to the damaging effects of filtered mid-UV radiation.

Adaptation, Physiological↗

Mixed high energy photon and electron radiation fields for calibrating radiation protection dosemeters.

According to ISO 4037-3, calibrations of radiation protection dosemeters with photon radiation of energies above 3 MeV are performed under conditions of charged particle equilibrium. No information is provided concerning how to determine the response of dosemeters to radiation fields in the more general case when these conditions are not fulfilled. This paper deals with the production of mixed high energy photon and electron fields characterised by a lack or an excess of charged particles relative to conditions of equilibrium and describes a new procedure for the dosimetry in such fields. Through variation of the charged particle fluence fraction with respect to a nearly constant photon fluence, Hp(10) and H'(10) values varied by up to a factor of 1.74. The above mentioned basic study was utilised in the recent IAEA intercomparison (Co-ordinated Research Project 1996-1998) and EURADOS 'trial performance test' (1996-1998) for individual monitoring of photon radiation in testing response characteristics of individual dosemeters in non-charged particle equilibrium conditions.

Air Pollution, Radioactive↗

Influence on cell proliferation of background radiation or exposure to very low, chronic gamma radiation.

Investigations carried out on the protozoan Paramecium tetraurelia and the cyanobacteria Synechococcus lividus, which were shielded against background radiation or exposed to very low doses of gamma radiation, demonstrated that radiation can stimulate the proliferation of these two single-cell organisms. Radiation hormesis depends on internal factors (age of starting cells) and external factors (lighting conditions). The stimulatory effect occurred only in a limited range of doses and disappeared for dose rates higher than 50 mGy/y.

Animals↗

A prospective study of differences in duodenum compared to remaining small bowel motion between radiation treatments: implications for radiation dose escalation in carcinoma of the pancreas.

PURPOSE: As a foundation for a dose escalation trial, we sought to characterize duodenal and non-duodenal small bowel organ motion between fractions of pancreatic radiation therapy. PATIENTS AND METHODS: Nine patients (4 women, 5 men) undergoing radiation therapy were enrolled in this prospective study. The patients had up to four weekly CT scans performed during their course of radiation therapy. Pancreas, duodenum and non-duodenal small bowel were then contoured for each CT scan. On the initial scan, a four-field plan was generated to fully cover the pancreas. This plan was registered to each subsequent CT scan. Dose-volume histogram (DVH) analyses were performed for the duodenum, non-duodenal small bowel, large bowel, and pancreas. RESULTS: With significant individual variation, the volume of duodenum receiving at least 80% of the prescribed dose was consistently greater than the remaining small bowel. In the patient with the largest inter-fraction variation, the fractional volume of non-duodenal small bowel irradiated to at least the 80% isodose line ranged from 1% to 20%. In the patient with the largest inter-fraction variation, the fractional volume of duodenum irradiated to at least the 80% isodose line ranged from 30% to 100%. CONCLUSION: The volume of small bowel irradiated during four-field pancreatic radiation therapy changes substantially between fractions. This suggests dose escalation may be possible. However, dose limits to the duodenum should be stricter than for other segments of small bowel.

Dose-Response Relationship, Radiation↗

Secondary carcinogenesis in patients treated with radiation: a review of data on radiation-induced cancers in human, non-human primate, canine and rodent subjects.

Concern for risk of radiation-induced cancer is growing with the increasing number of cancer patients surviving long term. This study examined data on radiation transformation of mammalian cells in vitro and on the risk of an increased cancer incidence after irradiation of mice, dogs, monkeys, atomic bomb survivors, occupationally exposed persons, and patients treated with radiation. Transformation of cells lines in vitro increased linearly with dose from approximately 1 to approximately 4-5 Gy. At <0.1 Gy, transformation was not increased in all studies. Dose-response relationships for cancer incidence varied with mouse strain, gender and tissue/organ. Risk of cancer in Macaca mulatta was not raised at 0.25-2.8 Gy. From the atomic bomb survivor study, risk is accepted as increasing linearly to 2 Sv for establishing exposure standards. In irradiated patients, risk of cancer increased significantly from 1 to 45 Gy (a low to a high dose level) for stomach and pancreas, but not for bladder and rectum (1-60 Gy) or kidney (1-15 Gy). Risk for several organs/tissues increased substantially at doses far above 2 Gy. There is great heterogeneity in risk of radiation-associated cancer between species, strains of a species, and organs within a species. At present, the heterogeneity between and within patient populations of virtually every parameter considered in risk estimation results in substantial uncertainty in quantification of a general risk factor. An implication of this review is that reduced risks of secondary cancer should be achieved by any technique that achieved a dose reduction down to approximately [corrected] 0.1 Gy, i.e. dose to tissues distant from the target. The proportionate gain should be greatest for dose decrement to less than 2 Gy.

Animals↗

Comparison of the X-radiation, drug and ultraviolet-radiation responses of clones isolated from a human colorectal tumor cell line.

We isolated several clones with a wide range of responses to X radiation from an unirradiated human colorectal (HCT 116) tumor cell line. The responses of one of these clones (HCT116-Clone10) and nine other clones to either fractionated or acute (i.e. single, nonfractionated doses) X irradiation in vitro was similar to that of the parental cell line. By contrast, after the same types of treatment, another clone (HCT116-Clone2) manifested a significantly increased survival whereas a third clone (HCT116-CloneK) manifested a significantly decreased survival relative to the parental cell line. This suggested that they were, respectively, a radioresistant and a radiosensitive clone. All three clones (clones 2, 10, K) retained their tumorigenic phenotype and formed tumors in nude mice. G-banding studies demonstrated that they were of human origin and were derived from the same parental cell line. The metaphases of HCT116-Clone2 demonstrated features commonly associated with genomic instability (i.e. mitotic catastrophe including chromosome and chromatid breaks, dicentrics and additional nonclonal markers). Data obtained by quantitative fluorescence in situ hybridization (Q- FISH) analysis failed to demonstrate any apparent correlation between the radiosensitivity and the relative telomere content of these three clones. Interestingly, HCT116-CloneK was the most resistant to several chemotherapeutic drugs (topotecan, camptothecin, etoposide and cisplatin) with diverse mechanisms of action. Also, there were no significant differences in the survivals of the three clones after treatment with UV radiation. Because of the lack of overlap among the relative sensitivities of these clones to X radiation, chemotherapeutic drugs and UV radiation, these clones may be useful models for evaluating the genetic basis of the response of human tumor cells to these treatment agents both in vitro and in vivo.

Antineoplastic Agents↗

[Evolution of radiation exposure to operator in diagnostic and interventional radiology procedures and reduction of radiation exposure to operator with protective device].

A study was performed to evaluate operator dose during diagnostic and interventional radiology procedures (IVR) and to establish methods of operator dose reduction with a radiation protective device. Operator dose was measured by glass dosimeters worn on the neck and on the abdomen outside the lead apron. In addition, the dose of the primary beam at the collimator surface was measured, which made it possible to define the correlation between the entrance air kerma, measured with Skin Dose Monitor, and operator dose exposed during the monitored procedure. IVR protectors were developed to decrease the amount of scatter radiation received by operators performing the procedures, and their effects were evaluated in abdominal and cardiac angiography procedures. The average effective dose and doses of the neck and abdomen outside the lead apron, estimated for individual procedures, were as follows: abdominal angiography procedures: effective dose, 0.07 mSv; neck area, 0.18 mSv; abdominal area, 0.51 mSv; cardiac angiography procedures: effective dose, 0.07 mSv; neck area, 0.13 mSv; abdominal area, 0.68 mSv. Operator doses were well correlated with exposure dose in abdominal angiography procedures (diagnostic procedure r=0.84, IVR r=0.77). It was found that 68.0% of the effective dose in abdominal angiography procedures and 43.0% of the effective dose in cardiac angiography procedures could be reduced by the use of IVR protectors. Operator and patient doses in interventional radiology were interdependent. The minimization of operator doses is particularly important during interventional radiology, and it is necessary to be aware of practical radiation protection procedures. Measures that reduce patient dose will also reduce occupational exposure. Moreover, operator dose could be substantially reduced by the use of IVR protectors in addition to wearing a protective lead apron during IVR. It was suggested that IVR protectors are effective radiation protective devices in interventional radiology procedures.

Angiography↗

[The model of the rate of radiation-induced mammalian death based on the determination of delayed consequences of different doses of radiation].

Analyzed were model descriptions of the probability of mammalian lethality and a possible life span reduction consequent to acute and chronic exposures to different dose rates. The proposed model of radiation rate of mammalian death links variations of the coefficient of mammalian death due to acute and prolonged radiation exposures with age. Application of the model to relevant experimental data yielded model coefficients for these periods of exposure. The radiation-modified dependence of lethality coefficients on age makes it possible to obtain fairly simple analytical expressions describing the survival probability long after exposure as a function of dose and dose rate, estimating radiation risk at any time point following exposure, and shortening of mean life span associated with exposure to different doses.

Acute Disease↗

Contribution of radiation-induced, nitric oxide-mediated bystander effect to radiation-induced adaptive response.

There has been a recent upsurge of interest in radiation-induced adaptive response and bystander effect, which are specific modes in stress response to low-dose/low-dose rate radiation. Recently, we found that the accumulation of iNOS in wtp53 celIs was induced by chronic irradiation with gamma rays followed by acute irradiation with X-rays, but not by each one, resulting in an increase in nitrite concentrations of medium. It is suggested that the accumulation of iNOS may be due to the depression of acute irradiation-induced p53 functions by pre-chronic irradiation. In addition, we found that the radiosensitivity of wtp53 cells against acute irradiation with X-rays was reduced after chronic irradiation with gamma rays. This reduction of radiosensitivity of wtp53 cells was nearly completely suppressed by the addition of NO scavenger, carboxy-PTIO to the medium. This reduction of radiosensitivity of wtp53 cells is just radiation-induced adaptive response, suggesting that NO-mediated bystander effect may considerably contribute to adaptive response induced by radiation.

Adaptation, Physiological↗

[Periods of cardiovascular diseases development in individuals with chronic radiation sickness caused mainly by external uniform radiation].

The author analysed files of 101 patients suffered from chronic radiation sickness due to chronic occupational mainly external radiation (dose of 98 to 947 cGy). Through represented clinical diagnoses, the author studied age of primary diagnosis of ischemic heart disease, cerebrovascular diseases in general and of individual entities, arterial hypertension, relationships between age at the diagnosis and total radiation dose, dose rate. The article presents comparative data on dose loads, time of various cardiovascular diseases diagnosis in accordance with circulatory disorders during chronic radiation sickness.

Aged↗

[A comparative evaluation of the changes in the duration of "hexenal sleep" in acute radiation and combined radiation-thermal lesions].

In experiments with Wistar rats it was found that the increase in the length of the "hexenal dream" during the first week after the effect of a mixture of radiation and heat is much more pronounced than that observed after exposure to radiation alone and independent of the severity of a radiation component (gamma radiation, 4, 6 and 7.5 Gy). The peculiarities revealed in the hypnotic effect of hexenal develop against the background of the postirradiation aggravation of hypoalbuminemia and decrease in the liver ATP.

Acute Disease↗

Radiation sensitivity of cell strains from families with genetic disorders predisposing to radiation-induced cancer.

This investigation was designed to test the hypothesis that skin fibroblasts from patients with genetic disorders characterized by hypersusceptibility to X-ray-induced cancer are sensitive to the cytotoxic or clastogenic effects of X-irradiation in vitro. Cell strains were established from 28 specifically ascertained patients from families with nevoid basal cell carcinoma syndrome, retinoblastoma, or other disorders apparently predisposing to radiation-induced cancer. These included 10 patients with a clear personal or family history of radiation-induced tumors. These cell strains were examined for the cytotoxic effects of X-irradiation in 3 distinct series of separate, blinded experiments, along with a group of 9 similarly coded cell bank controls. Cells from 11 of these patients and 6 controls were studied for sensitivity to X-ray-induced chromosomal aberrations. Seven of the 37 cell strains were moderately hypersensitive to radiation-induced cell killing; 2 of these were from patients with radiation-induced tumors and 1 was a cell bank control. These results suggest that such isolated cases of hypersensitivity probably do not relate to the underlying genetic disorder. Overall, the X-ray response of cells from affected individuals in this study showed no systematic difference from that of cells from nonaffected relatives or cell bank controls for either cytotoxicity or clastogenicity.

Adolescent↗

Radiation doses due to human exposure to cosmic radiation in the Republic of Croatia.

The annual per caput whole body equivalent dose for the world's population on ground level in areas on normal background from natural sources of radiation is approximately 2.4 mSv, 0.3 mSv of which is due to cosmic rays. As the intensity of cosmic radiation increases with altitude, the subpopulation of aircraft flight crews and frequent flyers may receive an additional equivalent dose of up to 1 mSv during commercial flights. The estimated annual collective equivalent dose from aircraft flights for the Republic of Croatia is about 4 man Sv, whereas the annual collective effective dose due to the cosmic radiation component of normal background radiation is approximately 1200 man Sv. Future development of hypersonic aircraft, which would fly orbital trajectories above the Earth's atmosphere would cause a significant increase of doses. Also, future utilization of extended space missions might be limited by high equivalent doses to space travellers.

Aerospace Medicine↗

[Method of calculating the probability of radiation-induced complications in organs and tissues in relation to volume of radiation and dose fractionation].

Mathematical models have been first developed, which describe the probability of radiation-induced complications of particular types as a function of the dose and volume of radiation and the scheme of dose fractionation in time. New mathematical models were derived from the synthesis of the mathematical models which describe the probability of radiation-induced complications for the fixed scheme of dose fractionation and which describe the equivalent schemes of dose fractionation for the fixed likelihood of radiation-induced complications.

Humans↗

[Assessing the degree of radiation hazards in the use of open radiation sources in scientific research institutions].

The hazard from the use of open radiation sources in scientific and scientific-and-practical activity was evaluated. The frequency and assortment of radionuclide uses in national economy is considered. Examining the working conditions, the radiation protection system for employees indicates that the staff is safe when the radiation level is 5 +/- 0.5 mSb/y. Recommendations for reducing radiation levels in the working areas are given.

Academies and Institutes↗

A space radiation shielding model of the Martian radiation environment experiment (MARIE).

The 2001 Mars Odyssey spacecraft was launched towards Mars on April 7, 2001. Onboard the spacecraft is the Martian radiation environment experiment (MARIE), which is designed to measure the background radiation environment due to galactic cosmic rays (GCR) and solar protons in the 20-500 MeV/n energy range. We present an approach for developing a space radiation-shielding model of the spacecraft that includes the MARIE instrument in the current mapping phase orientation. A discussion is presented describing the development and methodology used to construct the shielding model. For a given GCR model environment, using the current MARIE shielding model and the high-energy particle transport codes, dose rate values are compared with MARIE measurements during the early mapping phase in Mars orbit. The results show good agreement between the model calculations and the MARIE measurements as presented for the March 2002 dataset.

Computer Simulation↗