Dosimetric characteristics of a new polymer gel and their dependence on post-preparation and post-irradiation time: Effect on X-ray beam profile measurements

The aim of this study is to dosimetrically characterize a new MRI based polymer gel system and to evaluate its usefulness in clinical practice just in terms of beam profile measurements.Normoxic N-vinylpyrrolidone based polymer gel (VIPET) phantoms were produced and used in order to perform three main sets of experiments: a) dose–response evaluation and reproducibility experiments, b) experiments for the evaluation of sensitivity of dose characteristics on ‘gel manufacture – irradiation’ time interval and c) experiments for the evaluation of sensitivity of dose characteristics on ‘irradiation – MRscanning’ time interval. It has been shown that this gel system can be used in a wide dose-range of 0–60 Gy. It exhibits a linear dose–response in the dose-range of 2–35 Gy. Following the proposed manufacturing method the dose–response characteristics are reproducible. Moreover, it seems that the optimum ‘gel manufacturing – irradiation’ time interval is 1 day. However, a ‘gel manufacturing – irradiation’ time interval up to ～1 week can be safely used. The optimum ‘irradiation – MRscanning’ time interval in terms of dose–response sensitivity and dose resolution can be reliably ranged from 1 day to 3 weeks. Finally, X-ray beam profile gel-measurements were performed and found to be in satisfying agreement with corresponding small sensitive volume ion chamber measurements. VIPET gel dosimeters preserved the spatial integrity of the dose distribution during a time period of 50 days post-irradiation. The studied gel system can be safely used in clinical practice within the practical limitations found and described in this work.     

Repopulation kinetics in irradiated mouse lip mucosa: the relative importance of treatment protraction and time distribution of irradiations

The repopulation kinetics of the irradiated lip mucosa of mice has been investigated. Split-dose experiments showed that, in this tissue, repopulation starts within 3 days after the first irradiation and increases exponentially within 10 days. To assess the relative importance of protraction and distribution of irradiations as a function of time, 10 fractions were given in (1) 3 days (three irradiations per day with a 4-hr interval), (2) 11 days (daily fractions), or (3) two short courses, each consisting of five fractions given in 1.5 days separated by a rest period of 8 days, with an overall time of 11 days. The results show that by protracting the treatment from 3 to 11 days (with daily irradiations) repopulation accounts for recovery of approximately 13 Gy. Delivering the radiation in two short courses separated by a rest period leads to an additional recovery of approximately 5 Gy. The most plausible explanation for this observation is that repopulation is much more efficient during the rest period between the two courses than during continuous daily irradiation. Although the regimen of two short courses with a rest period spares the acute reaction, it will not enhance the late tolerance. Before thorough knowledge about the repopulation kinetics of the tumors can be gained, caution should be observed for indiscriminate use of split-course multiple-fraction-per-day (MFD) regimens for treating various tumors.     

Response of a brachytherapy model using 125I in a murine tumor system

The effects of low-dose-rate irradiation (brachytherapy) were investigated in vivo using a murine mammary adenocarcinoma (MTG-B) growing in the flank of C3H mice. For local tumor irradiations, a noninvasive cap was devised to cover the tumor and house three 125I seeds (average apparent activity 5.2 mCi each) located at 120 degree intervals around the circumference of the hemispherical cap (13 mm i.d.). Mice were secured during treatment in a tube allowing limited mobility while restricting access to the seeds. Tumors were exposed to a series of dose rates ranging from 14-40 cGy/h, and the total dose over the treatment interval (48 or 72 h) ranged from 830 to 2378 cGy. A total of nine experiments were conducted using the caps over a 10-week interval. In each experiment three groups (irradiated tumors, sham controls, and untreated controls) were analyzed, each containing 8-15 mice (N = 34, untreated control; N = 46, sham control; N = 91, brachytherapy irradiation). The brachytherapy results are compared to the effects of external beam irradiation in the same tumor system. A linear relationship was observed between the total radiation dose and doubling volume growth delay (GDDV) or treatment volume growth delay (GDTV) for the brachytherapy and external beam irradiation. The slopes of the dose-response curves are steeper for the acute dose (517 cGy/min) external beam irradiation (0.0072 day/cGy, GDDV; 0.00695 day/cGy, GDTV) than for the brachytherapy (0.0050 day/cGy, GDDV; 0.0057 day/cGy, GDTV) using both GDTV and GDDV end points. Comparison of the tumor volume regrowth slopes indicates that the tumor bed effect is larger for external beam irradiation than for brachytherapy, suggesting that the tumor bed effect may be dose-rate dependent.     

Recovery responses in the bodies of rats following irradiation with microwaves (2400 MHz)

During microwave irradiation (SHF-field, 2400 Mc/s) of rats in the range of capacity density of from 100 mW/cm2 to 800 mW/cm2 the function of regenerative effect and the time interval between the irradiation cycles (power densityconst) approximates the logistic one, whereas that of the power density and the time interval between the irradiation cycles (regeneration level = const) approximates the linear one.     

A longitudinal study of radiation-induced changes in tumor vasculature by contrast-enhanced magnetic resonance imaging

Dynamic contrast-enhanced MRI with two different-sized contrast agents, Gd-DTPA and Gadomer-17, was used to study the effects of radiation on the pharmacokinetics of the paramagnetic enhancement of water relaxation in the rat R3230 AC adenocarcinoma tumor model. The kinetics of enhancement was analyzed by a two-compartment pharmacokinetic model to derive parameters related to vascular volume (V(b)) and permeability (K(2)). Rats implanted with tumors were divided into two groups; one received 5 Gy and the other received 20 Gy (137)Cs gamma rays. Sequential dynamic contrast-enhanced MRI studies were performed, one before irradiation, one at day 1 after irradiation, and another at day 3 after irradiation, to investigate the effect of the radiation dose and the changes that occurred over time. The analysis was performed on a pixel-by-pixel basis to study the heterogeneity within the tumor. The pixel distribution profiles of V(b) and K(2) from each tumor were obtained to assess the regional radiation-induced effects on vascular volume and permeability. No significant change in vascular volume was detected with either Gd-DTPA or Gadomer-17 after irradiation of the tumor; however, a small dependence of K(2) on the radiation dose was observed. After low-dose (5 Gy) irradiation, the mean value of K(2) decreased by 46% at day 1 compared to the baseline, presumably due to cell swelling, and decreased further by 67% from the baseline on day 3. When the dose was increased to 20 Gy, the mean value of K(2) measured with Gadomer-17 did not show any significant changes at either day 1 or day 3 after irradiation. The value of K(2) measured with Gd-DTPA did not show any significant changes after either the low or the high radiation dose.     

The influence of G2 progression on X-ray sensitivity of two-cell mouse embryos

Naturally synchronous, two-cell mouse embryos were X-irradiated in vitro. In experiment 1, irradiation was either in the early or in the late G2 phase, which lasts about 14 hours. In experiment 2, irradiation of all the embryos was in late G2 but embryos with different intervals between irradiation and the first mitosis after irradiation were separated and investigated independently. After 2 Gy the time interval between irradiation in late G2 and the first mitosis post-irradiation was on the average about 9 hours; after irradiation in the early G2 phase about 13.5 hours. Development (hatching of blastocysts) and cell proliferation (cell number per embryo at the stage of the hatched blastocyst) was most impaired and the frequency of micronuclei (determined in four- or eight-cell embryos) was highest in the case of a short interval between irradiation in G2 and the first mitosis post-irradiation. It is concluded that a longer interval allows a longer period of DNA repair. The results also demonstrate a positive correlation between the extent of chromosomal damage (micronuclei) and the extent of cell death as well as the impairment of the development of the whole biological system.     

Changes in antibacterial and proteolytic activity of polymorphonuclear leucocytes following the whole body x-irradiation of rabbits

In whole body x-irradiated rabbits with 150 r, 500 r and 1000 r an antibacterial and proteolytic activity in extracts of polymorphonuclear leucocytes obtained from peritoneal exudate was tested immediately and 1, 3, 6, 10 and 21 days following irradiation. The changes in antibacterial activity tested inEscherichia coli, Bethesda andSalmonella adelaide strains depended on the intensity of radiation and time interval between radiation and collection of leucocytes. With increasing radiation the antibacterial activity inBethesda andSalmonella adelaide strains was decreased. In rabbits irradiated 150 r and 500 r a decrease or even a disappearance of bactericidal activity on the sixth day in all strains tested was found, whereas after an irradiation with 1000 r the antibacterial activity was found to be low immediately after irradiation and this decrease could be detected up to the tenth day. UsingEscherichia coli strains the antibacterial activity of leucocyte extracts did not show such a regular dependence on the intensity of radiation and time as with other strains used. The proteolytic activity of leucocyte extracts tested at pH 3.5 (cathepsin D and E) and pH 2.0 (cathepsin E) within 3 days after irradiation was higher with increasing radiation. At other time intervals the activity did not show regular changes. The dynamics of changes in proteolytic activity at both pH was different and also a relation between proteolytic and antibacterial activity was not found.     

Hypofractionated irradiation of the solid form of Ehrlich ascites carcinoma in mice by a thin scanning proton beam

The dynamics of the growth of Ehrlich ascites carcinoma in mice of the SHK line exposed to hypofractionated high-dose irradiation by a thin scanning proton beam has been analyzed for different irradiation volumes and different time intervals (from 4 to 24 hours) between two 30-Gy fractions. Irradiation of the gross tumor volume and the planned target volume was performed within the Bragg peak; the energy of protons at the outlet of the accelerator ranged from 85 to 100 MeV. Hypofractionated irradiation of the gross tumor volume of Ehrlich ascites carcinoma resulted in a more pronounced antitumor effect than the irradiation of the planned target volume. The effect did not depend on the interval between the irradiation episodes.     

The effect of autoblood in a hyposmotic state on the colony-forming activity of hematopoietic stem cells]

It has been shown that hypoosmotic autoblood injected sub- or intracutaneously stimulates the colony-forming activity of haemopoietic stem cells in mice. Autoblood injected to animals immediately after their irradiation stimulates haemopoiesis even after a single dose. When mice are injected with autoblood prior to irradiation, the time between the first injection and the day of irradiation is critical for manifestation of the immunomodulating effect. Autoblood infusions immediately before, the day before, or two days before irradiation markedly deteriorate the clinical status of experimental animals and cause death in some of them. It is suggested that stimulation of haemopoiesis is associated with the appearance in the blood stream of a population of radiosensitive cells, apparently T-cell precursors.     

甜瓜幼苗叶片光合变化特性

为探讨甜瓜光响应变化特性与环境因子的关系,选择光响应曲线适宜测定的时段,以甜瓜幼苗为试材,将1 d分为3个时段:10:00-12:00、12:00-15:00和15:00-17:00,每个叶位叶片测定1 d,并采用直角双曲线修正模型拟合光响应曲线,研究不同时段下甜瓜叶片光响应曲线、光响应参数的变化趋势和不同叶位叶片光响应参数特性。结果表明:当环境中光合有效辐射增强,叶面温度(Tl)升高,空气相对湿度(RH)降低;当环境中光合有效辐射减弱,Tl降低,RH升高。10:00-12:00光响应曲线和12:00-15:00的第1-4叶光响应曲线呈双曲线,在强光下趋向饱和状况,12:00-15:00的第5叶光合速率和15:00-17:00光合速率在强光下出现明显的光抑制现象。1 d的不同时段均表现为10:00-12:00最大净光合速率(P_max)和光饱和点(LSP)最高,12:00-17:00降低;12:00-15:00光补偿点(LCP)和暗呼吸速率(R_d)较高,其它两个时段较低,10:00-17:00光补偿点量子效率(φ_c)、气孔导度(G_s)和胞间CO₂浓度(C_i)总体呈降低趋势,气孔限制值(L_s)升高。10:00-15:00相同时段测得的不同叶位叶片光响应参数,以第4-5叶光合性能较好,15:00-17:00以第3叶P_max最高,第5叶次之;10:00-17:00 G_s和C_i以第5叶较低,第1叶较高,L_s以第5叶较高,第1叶较低。RH为影响P_max的主要决策因子,测定时段、叶面饱和蒸汽压亏缺(Vpdl)和Tl为主要限制因子。10:00-12:00适宜进行光响应曲线测定,气孔限制为不同时段光合作用不同的主要因素,非气孔限制为影响不同叶位叶片光合作用的主要因素。     

Tissue repair and repopulation in the tumor bed effect

These experiments were designed to study the kinetics and magnitude of cell repair and repopulation in tissues whose damage results in the tumor bed effect. The right hind thighs of mice were irradiated with single doses or two equal gamma-ray fractions. Interfraction intervals ranging from 30 min to 24 h (to measure the kinetics of repair from sublethal damage) and 6 and 12 weeks (to determine the extent of repopulation) were used. One day after the second radiation dose 5 X 10(5) FSA tumor cells were inoculated into the center of the irradiated field. Radiation dose-response curves were obtained by calculating the time required for tumors to reach 12 mm diameter. No recovery occurred within 6 h of the radiation delivery as measured by this assay. Some recovery, 3.2-4.6 Gy above a single radiation dose, occurred when the interval between two fractions was 24 h. With increasing interfraction intervals of 6 and 12 weeks further dose sparing occurred in the amount of 5.0-6.9 and 7.5-8.3 Gy, respectively. The data suggest that repopulation is the major contributor to the radiation dose-sparing recovery of stromal tissue and that some proliferative response may occur as early as 1 day after the first irradiation.     

He–Ne laser (632.8 nm) pre‐irradiation gives protection against DNA damage induced by a near‐infrared trapping beam

We report the results of a study carried out to investigate the effect of He–Ne laser (632.8 nm) pre‐irradiation on DNA damage induced by continuous wave 1064 nm trapping beam exposure in MCF‐7 cells. A significant decrease in % tail DNA (p < 0.05) was observed in MCF‐7 cells pre‐exposed to He–Ne laser beam. The dependence of the induced protection against 1064 nm trapping beam irradiation induced DNA damage on the time interval between the two irradiations as well as the He–Ne laser pre‐irradiation parameters is presented. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

THE EFFECT OF A MEDIUM DOSE (430 ROENTGENS) OF X-RAY IRRADIATION ON RESTING CELLS OF THE LIVER

The mitotic activity of regenerating liver cells after a single dose (430 r) of x-ray irradiation was studied. In every group of the experimental animals (white rats), the mitotic activity (mitotic index) and the number of abnormal mitotic figures were determined. The results indicated that resting cells irradiated a short time before mitotic activity showed reactions similar to those of cells irradiated during mitotic activity. The disturbances in the irradiated mitotically active cells were only quantitatively different from those in the irradiated resting cells. The disturbances in the irradiated resting cells depended upon the time interval between the irradiation and the beginning of mitotic activity stimulated by partial hepatectomy. It was found that the shorter the time interval, the more pronounced were the disturbances and the more similar they became to those of irradiated mitotically active cells. Conversely, the longer the time interval between the irradiation and the beginning of mitotic activity, the less pronounced were the disturbances and the more similar they became to those of the non-irradiated control cells. A discussion is presented as to whether or not the lesions of resting cells caused by a single medium dose of x-ray irradiation are reversible, and whether such lesions are only brought to light by the process of mitosis or whether the process of mitosis renders it possible for these lesions to develop.     

Light and nitrate interaction in phytochrome-controlled germination ofPaulownia tomentosa seeds

Pulsed light and nitrate exhibit an interactive effect on the germination ofPaulownia tomentosa Steud. seeds that require long periods of light irradiation. Two pulses of red light (R), separated by an adequately long dark interval, substitute for continuous prolonged irradiation. A far-red (FR) pulse given at the beginning of the dark interval inhibits germination, while it has no effect if given at the end. The requirement for certain ratios of the far-red-absorbing form of phytochrome/total phytochrome (P_fr/P_tot) differs when a FR+R-pulse is given as the first or second of two pulses (FR+R or R) separated by a dark interval. An equal decrease of the P_fr/P_tot ratio leads to a more pronounced decrease in germination when the pulse of the same FR+R ratio is given as the second pulse at the end of the dark interval. The length of dark interval between light pulses needed for maximal germination, differed in (i) seeds with a natural requirement for long periods of light irradiation from that in (ii) seeds with their long light requirement imposed by two weeks of imbibition in darkness or by (iii) imbibition in 40% heavy water. However, a single R pulse was sufficient to induce a high percentage of germination if the seeds were supplied with KNO₃ (10 mM) from the onset of imbibition up to the onset of light. This effect decreased with a delayed time of application, and was prevented if FR preceded the KNO₃ application. We dedicate this paper to Professor Hans Mohr on the occasion of his 60th birthday     

The effect of continuous irradiation on cell proliferation and maturation in small intestinal epithelium.

Autoradiographic studies and scintillation counting of crypt material after pulse labelling with 3H-thymidine showed that during continuous irradiation with 290 rads/day a reduced proliferative activity is present in the crypts of rat small intestine after 1 day of irradiation and of normal activity during the remaining period (5 days) irradiation. After cessation of irradiation an increase in proliferative activity can be observed after 1 day of recovery. From the time (36-48 hr after starting of the irradiation) that the number of villus cells is reduced an expansion of the proliferation zone in the crypt was observed. Both effects last until 1 day of recovery after cessation of irradiation. The process of crypt cell maturation and of villus cell function has also been studied during and after continuous irradiation by micro-chemical enzyme analyses in isolated crypts and villi. It was found that the expansion of the proliferation zone in the crypt is accompanied by a decrease in activity of only those enzymes (i.e. non-specific esterases) which normally become active during crypt cell maturation. The activity of enzymes normally present mainly in the functional villus cells remained relatively unaffected by changes in crypt cell kinetics. A hypothesis of different regulation mechanisms of the proliferative activity in the intestinal crypt and a possible explanation of the different behaviour of various enzyme activities as a result of changes in crypt cell proliferation is discussed.     

THE EFFECT OF CONTINUOUS IRRADIATION ON CELL PROLIFERATION AND MATURATION IN SMALL INTESTINAL EPITHELIUM

Autoradiographic studies and scintillation counting of crypt material after pulse labelling with ³H-thymidine showed that during continuous irradiation with 290 rads/day a reduced proliferative activity is present in the crypts of rat small intestine after 1 day of irradiation and of normal activity during the remaining period (5 days) irradiation. After cessation of irradiation an increase in proliferative activity can be observed after 1 day of recovery. From the time (36–48 hr after starting of the irradiation) that the number of villus cells is reduced an expansion of the proliferation zone in the crypt was observed. Both effects last until 1 day of recovery after cessation of irradiation. The process of crypt cell maturation and of villus cell function has also been studied during and after continuous irradiation by micro-chemical enzyme analyses in isolated crypts and villi. It was found that the expansion of the proliferation zone in the crypt is accompanied by a decrease in activity of only those enzymes (i.e. non-specific esterases) which normally become active during crypt cell maturation. The activity of enzymes normally present mainly in the functional villus cells remained relatively unaffected by changes in crypt cell kinetics. A hypothesis of different regulation mechanisms of the proliferative activity in the intestinal crypt and a possible explanation of the different behaviour of various enzyme activities as a result of changes in crypt cell proliferation is discussed.     

Proliferative activity of Shvetz tumor following single and repeated irradiation]

Autoradiographic study of an experimentally-induced tumour following local irradiation in a dose of 600 rad showed no retardation of the cell cycle 6 to 12 hours after the irradiation. Marked reduction of the mitotic index (MI) and of the labeled nuclei index (LNI) was noted to the 96th hour after the irradiation. In repeated irradiation in a dose of 1200 rad at an interval of 18 hours there was revealed a marked reduction of the MI and of the LNI as a result of the block of the passage of cells from the G1-period into S. However, restoration of the cell proliferation uas noted by the 24th-48th hours. A high MI revealed at all the periods of investigation after repeated tumour irradiation at an interval of 24 hours was possibly caused by an increase in the time of mitosis proper, this also being confirmed by a significant accumulation of the number of late mitotic phases.     

Semiquantitative detection of cytokine messages in X-irradiated and regenerating rat thymus

We investigated the expression of cytokine mRNA derived from thymocytes or thymic epithelial cells in X-irradiated (8 Gy) and recovering rat thymuses, according to our previous observation (Mizutani et al., Radiat. Res. 157, 281-289, 2002). The changes in mRNA expression level of interleukin 2 (Il2), Il4, tumor necrosis factor alpha (Tnf), interferon gamma (Ifng), and transforming growth factor beta (Tgfb) were examined. The mRNA expression of Il2 and Il4 decreased from day 5 to day 14 after irradiation. Thereafter, the expression level of Il2 mRNA recovered to normal control levels; however, the expression of Il4 mRNA tended toward significantly low levels. Tnf mRNA expression decreased on day 5 after irradiation and then showed a gradual increase back to normal control levels. Tgfb mRNA expression did not change significantly. Ifng mRNA expression was transiently enhanced from day 11 to day 14. The mRNA expression levels of Il10 increased significantly from day 3 to day 7 after irradiation. In addition, the mRNA expression of thymic epithelial cell-derived Il7 showed a transient decrease on day 3; however, then it showed a continuous increase from day 5 to day 21, finally reaching twice the normal control levels after X irradiation. These observations suggest that the expression of cytokine messages in the irradiated thymus changed significantly and did not return to normal for a long time after 8 Gy irradiation.     

The Effect of High Intensity Interval Exercise on Postprandial Triacylglycerol and Leukocyte Activation – Monitored for 48h Post Exercise

Postprandial phenomenon are thought to contribute to atherogenesis alongside activation of the immune system. A single bout of high intensity interval exercise attenuates postprandial triacylglycerol (TG), although the longevity and mechanisms underlying this observation are unknown. The aims of this study were to determine whether this attenuation in postprandial TG remained 2 days after high intensity interval exercise, to monitor markers of leukocyte activation and investigate the underlying mechanisms. Eight young men each completed two three day trials. On day 1: subjects rested (Control) or performed 5 x 30 s maximal sprints (high intensity interval exercise). On day 2 and 3 subjects consumed high fat meals for breakfast and 3 h later for lunch. Blood samples were taken at various times and analysed for TG, glucose and TG-rich lipoprotein (TRL)-bound LPL-dependent TRL-TG hydrolysis (LTTH). Flow cytometry was used to evaluate granulocyte, monocyte and lymphocyte CD11b and CD36 expression. On day 2 after high intensity interval exercise TG area under the curve was lower (P<0.05) (7.46±1.53 mmol/l/7h) compared to the control trial (9.47±3.04 mmol/l/7h) with no differences during day 3 of the trial. LTTH activity was higher (P<0.05) after high intensity interval exercise, at 2 hours of day 2, compared to control. Granulocyte, monocyte and lymphocyte CD11b expression increased with time over day 2 and 3 of the study (P<0.0001). Lymphocyte and monocyte CD36 expression decreased with time over day 2 and 3 (P<0.05). There were no differences between trials in CD11b and CD36 expression on any leukocytes. A single session of high intensity interval exercise attenuated postprandial TG on day 2 of the study, with this effect abolished by day 3.The reduction in postprandial TG was associated with an increase in LTTH. High intensity interval exercise had no effect on postprandial responses of CD11b or CD36.     

Effects of hyperthermia and X-irradiation on mouse stromal tissue

The sensitivity of normal stroma to heat, irradiation and heat combined with irradiation has been studied using the tumour bed effect (TBE) assay. Irradiation before implantation led to a TBE. This TBE was dose dependent below 15 Gy, the TBE remaining relatively constant above 15 Gy. The interval (0-90 days) between irradiation and tumour implantation did not influence the magnitude of the TBE. Hyperthermia with large heat doses (45-60 min at 44 degrees C) before implantation may lead to a TBE. The interval between hyperthermia and tumour implantation proved to be very important. Our results show that the recovery from heat-induced stromal damage is very rapid. When the interval between hyperthermia and tumour implantation is 10 days or longer, no TBE could be observed. Irradiation combined with large heat doses (30-60 min at 44 degrees C) decreased the radiation-induced TBE. However, the combination of irradiation with mild heat treatments (15 min at 44 degrees C) could lead to a larger TBE than after irradiation alone. When hyperthermia was given prior to irradiation, the interval between heat and irradiation proved to be very important. With large intervals (21 days or longer) the TBE values were about the same as with irradiation alone. When heat was given after irradiation it always reduced the irradiation-induced TBE.