A functional and chemical study of radiation effects on rat parotid and submandibular/sublingual glands.

The aim of this study was to monitor composition and rate of secretion of rat parotid and submandibular/sublingual saliva following local single doses of X-rays ranging from 5 to 20 Gy. Pilocarpine-stimulated samples of parotid and submandibular/sublingual saliva were simultaneously collected with miniaturized Lashley cups before and 1-30 days after irradiation. The lag phase (period between injection of pilocarpine and start of the secretion) and flow rate were recorded and the concentrations of sodium, potassium, calcium, phosphate, and amylase were measured. With increasing dose and time, the salivary flow rate as well as sodium concentration decreased, while potassium concentrations increased throughout the follow-up period. The lag phase and the concentration of amylase reached their maximum at 3 and 10 days after irradiation, respectively. The changes in lag phase and flow rate were most obvious after doses of 15 or 20 Gy and showed a great similarity for parotid and submandibular/sublingual saliva. No dose-response relationship was observed for the changes in concentrations of calcium and phosphate. It is concluded that for radiation doses of 10 Gy and above, irreversible changes (lag phase, flow rate, potassium, sodium) were observed. A saturation of the irradiation effects (lag phase, flow rate) seems to exist at doses larger than 15 Gy. No significant differences were observed between the radiation-induced functional changes in parotid and submandibular/sublingual salivary gland tissue.     

Repopulation kinetics of rat rhabdomyosarcoma tumors following single and fractionated doses of low-LET and high-LET radiation

Measurements were made of clonogenic cell survival in rat rhabdomyosarcoma tumors as a function of time following in situ irradiation with single or fractionated doses of 225-kVp X rays or with 557-MeV/u neon ions in the distal position of a 4-cm extended-peak ionization region. Single doses of 20 Gy of X rays or 7 Gy of peak neon ions reduced the initial surviving fraction to approximately 0.025 for each modality. Daily fractionated doses (four fractions in 3 days) of either peak neon ions (1.75 Gy per fraction) or X rays (6 Gy per fraction) achieved a cell survival of approximately 0.02-0.03 after the fourth dose of radiation. In the single-dose experiments, significant 5- and 10-fold decreases in the fraction of clonogenic cells were observed between the third and fourth days after irradiation with peak neon ions and X rays, respectively. After the sixth day postirradiation, the residual clonogenic cells exhibited a rapid burst of proliferation leading to doubling times for the surviving cell fractions of approximately 1.5 days. Radiation-induced growth delay was consistent with the cellular repopulation dynamics. In the fractionated-dose experiments with both radiation modalities, a large delayed decrease in cell survival was observed at 1-3 days after completion of the fractionated-dose schedule. Cellular repopulation was consistent with postirradiation tumor volume regression and regrowth for both radiation modalities. The extent of decrease in survival following the four-fraction radiation schedule was approximately two times greater in X-irradiated than in neon-ion-irradiated tumors that produced the same survival level immediately after the fourth dose. Mechanisms underlying the marked reduction in cell survival 3-4 days postirradiation are discussed, including the possible role of a toxic host cell response against the irradiated tumor cells.     

Nonuniform irradiation of the canine intestine. I. Effects

To investigate the effects of nonuniform irradiation on the small intestine, we prepared 24 dogs for continent isoperistaltic ileostomies under aseptic surgical conditions and general anesthesia. After a 3-week recovery period, the ileum was catheterized with a fiberoptic endoscope to observe the intestinal mucosa and to harvest mucosal biopsies. The baseline macroscopic and microscopic appearance of the intestinal mucosa was determined. Two weeks later, the ileum was catheterized with a 100-cm soft tube containing 40 groups of three thermoluminescent dosimeters placed at equally spaced intervals, and a dose of either 4.5, 8, 10, 11, or 15 Gy 60Co gamma rays was delivered to the right abdomen (nonuniform exposure). This method allowed a direct and precise assessment of the dose received at 40 sites located in the 100-cm intestinal segment. The intestinal mucosa was again evaluated 1, 4, and 6 days after irradiation. All animals exposed to 4.5 and 8 Gy survived, whereas none survived after 11 and 15 Gy. After exposure to 10 Gy, 60% of the animals died within 4-6 days and 40% survived with symptoms associated with both the intestinal and the hematopoietic syndromes. Crypt cell necrosis, blunting of villi, and reduction of the mucosal lining increased between 1 and 4 days after irradiation, and mucosal damage was correlated with intraintestinal dosimetry at Day 6. The granulocyte counts at Day 4 were significantly lower than baseline level in animals that died within 4-6 days but not in survivors. The present model appears to be realistic and clinically relevant, allowing the concurrent study of the intestinal and hematopoietic effects of high-dose nonuniform irradiation similar to that received by patients during radiation therapy as well as by radiation accident victims.     

Progressive development of radiation damage in mouse kidneys and the consequences for reirradiation tolerance

The aim of this study was to investigate the influence of protracted overall treatment times on the development and repair of renal irradiation injury in mice. Functional kidney damage was measured, from the proportion of 51CrEDTA remaining in the plasma at 30 min after injection of the tracer. Damage was assessed at monthly intervals for up to 14 months after two equal doses of X-rays given in 1 day, 1 month or 6 months. There was no difference between the time of onset or rate of development of damage after two fractions in 1 day or 1 month, but there was a time lag of 7-15 weeks (depending on dose) before the development of damage after 2F given in 6 months. After this time lag the rate of progression of damage was the same for 2F/6 months as for 2F in the shorter intervals. There was therefore no indication of any increase in total tolerated dose for the kidney when the treatment time was protracted, although the time scales for onset of this damage differed. Tolerance of mouse kidneys to reirradiation at 6 months after single doses of 6-12 Gy was also assessed. All of the previously irradiated animals developed a more severe renal impairment after reirradiation than did the age-matched control mice. The most severe damage occurred in mice which received the highest initial radiation doses, but doses of only 6 Gy were sufficient to markedly reduce the tolerance to reirradiation. It was concluded from these studies that no additional dose-sparing (tissue recovery) took place in the kidneys during a 6-month interval. This was true even when the initial radiation dose alone was insufficient to cause measurable renal dysfunction.     

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.     

The repair of potentially lethal damage and sublethal damage in strains of mouse L5178Y lymphoma cells differing in radiation sensitivity

Mouse lymphoma strains L5178Y-R (LY-R) and L5178Y-S (LY-S), which are differentially sensitive to the cytotoxic effects of ionizing radiation, were found to differ in their abilities to repair potentially lethal damage (PLD) and sublethal damage (SLD). The results showed that strain LY-R was more proficient than strain LY-S in the repair of SLD. The split dose recovery observed in strain LY-S could be accounted for by its recovery during postirradiation incubation. In contrast, SLD repair occurred in the absence of PLD repair in strain LY-R. The possibility that the repair of PLD might be completed prior to the postirradiation incubation in strain LY-R was suggested by the decreased survival observed when the cells were irradiated in a hypotonic solution. The repair of PLD and SLD in strain LY-S was temperature sensitive, occurring during postirradiation incubations between 15 and 34 degrees C, but not at 37 or 40 degrees C. This temperature sensitivity is very similar to the temperature sensitivity of the repair of pH 9.6-labile lesions in DNA in strain LY-S, as reported previously. Thus postirradiation cellular recovery processes in strain LY-S may involve the repair of pH 9.6-labile lesions in DNA. Temperature-dependent changes in the postirradiation distribution of cells throughout the cell cycle were observed which could contribute to the temperature sensitivity of the postirradiation recovery of strain LY-S.     

Radiation effects on diamine oxidase activities in intestine and plasma of the rat

Diamine oxidase (DAO; EC 1.4.3.6) activity was measured in plasma and in ileal tissue homogenates prepared from male Sprague-Dawley rats euthanized at 1-15 days after acute whole-body irradiation with 14.5-MeV electrons. Animals irradiated with 1 Gy showed no diminution in plasma and ileal DAO activities through Day 13 relative to nonirradiated controls. Animals irradiated with 5, 10, and 12 Gy displayed marked declines in ileal DAO activity, with levels reaching a nadir on Day 3. This was paralleled by a decrease in plasma DAO activity in all three dose groups. Recovery of ileal and plasma DAO levels was later seen as early as Day 4 in animals irradiated with 5- and 10-Gy doses, but animals receiving 12 Gy did not survive beyond Day 3. The relationship between radiation dose and levels of plasma and ileal DAO on Day 3, the time of maximum decrease at all doses, was also investigated. Ileal DAO activity decreased almost linearly between 2 and 8 Gy. Plasma DAO activity closely paralleled the dose dependency of the ileal levels. These data suggest that plasma DAO activity might be useful as a biologic marker of intestinal epithelial injury and recovery after acute radiation exposure.     

Perinatal changes in amylase and serum corticosterone levels in rats

In rats amylase activity in the pancreas increased greatly from day 15 of gestation to a maximum on day 21. Then it decreased to less than one-tenth of this maximum value on about day 5 after birth. It increased again about 15 days after birth and reached the adult level about 30 days after birth.No amylase activity was in the parotid gland before birth: it appeared about 12 days after birth and reached the adult level, which was higher than that in the pancreas, about 30 days after birth.The serum corticosterone level was as high as the adult level before birth. Then it decreased to less than one-tenth of the adult level 5 days after birth and increased again from 15 to 25 days after birth to the adult level. The developmental change in the serum corticosterone level seemed to influence amylase activity in the pancreas both before and after birth, and that in the parotid gland only after birth.The serum contained both pancreatic and paratoid type isozymes of amylase until 1 day after birth but only the parotid type from 3 days after birth.     

Regional blood-to-tissue transport in an irradiated rat glioma model

To assess vascular permeability in intracerebral grafts of the 36B-10, F-344 rat glioma following 20 Gy 137Cs whole brain irradiation, the blood-to-tissue transport constant, K, of [14C]-alpha-aminoisobutyric acid (AIB) was measured with quantitative autoradiography. Mean, 90th percentile, and 95th percentile values of K were determined in individual tumors and in treatment groups. In 15-day-old unirradiated control tumors, mean, 90th percentile, and 95th percentile values of K were, respectively, 11.3, 18.4, and 20.8 ml kg-1 min-1. In 15-day-old tumors irradiated on Day 14 (Day 1 postirradiation tumors) the K values were 5.9, 9.4, and 10.4, all of which were significantly less than the respective control values (P less than 0.01). In 16-day-old tumors irradiated on Day 14 (Day 2 postirradiation tumors), the K values were 10.8, 15.0, and 16.0, respectively, none of which was significantly different from control tumors. Mean K values for Day 2 vs Day 1 postirradiation tumors (10.8 vs 5.9) yielded P less than 0.05, but the 90th percentile and 95th percentile values for Day 2 vs Day 1 yielded 0.05 less than P less than 0.10. Separate experiments measured AIB and 86RbCl uptake in 36B-10 cells in vitro 1 and 2 days following 20 Gy irradiation to assess whether this radiation dose reduced the capacity of tumor cells to trap AIB or Rb+. Irradiation did not reduce the accumulation of either tracer, but rather was associated with an increased accumulation of AIB. Therefore, the AIB transport data suggest that vascular permeability and/or surface area decreases significantly in the day following 20 Gy irradiation and that this decrease reverses by the second day following irradiation.     

The effects of ionizing radiation on the pulmonary vasculature of intact rats and isolated pulmonary endothelium

We studied the effects of ionizing radiation on the morphology of the pulmonary circulation using an in vivo rat model and an in vitro pulmonary artery endothelial cell model. Gamma radiation was given as either an acute (30 Gy) or fractionated (5 X 6 Gy) dose to one hemithorax of rats. An acute 30-Gy dose delivered resulted in a 70% decrease in pulmonary arterial perfusion, using technetium-99m microaggregated albumin (99mTc-MAA), in the irradiated lung by 2-3 weeks after irradiation. Pulmonary microradiographs, using a barium sulfate perfusion method, obtained 2-3 weeks after irradiation demonstrated widespread loss of capillary filling and segmentation of the vessels. Histologic examination demonstrated intact capillaries, suggesting that the alterations in pulmonary perfusion were at the precapillary level. Similar abnormalities in lung perfusion and morphology were found after delivery of fractionated doses of radiation, but the onset of the changes was delayed, occurring 4-6 weeks postirradiation. Using cultured pulmonary endothelial cell monolayers, cell sloughing and retraction from the surface substrate were observed within 24 h after in vitro delivery of 30 Gy. Similar findings occurred in monolayers given fractionated doses (5 X 6 Gy) of radiation 2-3 days after the final dose. The in vivo animal and in vitro endothelial cell models offer a useful means of examining the morphologic alterations involved in radiation lung vascular damage.     

Influence of ginger rhizome (Zingiber officinale Rosc) on survival, glutathione and lipid peroxidation in mice after whole-body exposure to gamma radiation

The radioprotective effect of the hydroalcoholic extract of ginger rhizome, Zingiber officinale (ZOE), was studied. Mice were given 10 mg/kg ZOE intraperitoneally once daily for five consecutive days before exposure to 6-12 Gy of gamma radiation and were monitored daily up to 30 days postirradiation for the development of symptoms of radiation sickness and mortality. Pretreatment of mice with ZOE reduced the severity of radiation sickness and the mortality at all doses. The ZOE treatment protected mice from GI syndrome as well as bone marrow syndrome. The dose reduction factor for ZOE was found to be 1.15. The optimum protective dose of 10 mg/kg ZOE was 1/50 of the LD50 (500 mg/kg). Irradiation of the animals resulted in a dose-dependent elevation in the lipid peroxidation and depletion of GSH on day 31 postirradiation; both effects were lessened by pretreatment with ZOE. ZOE also had a dose-dependent antimicrobial activity against Pseudomonas aeruginosa, Salmonella typhimurium, Escherichia coli and Candida albicans.     

Comparative developmental analysis of the parotid, submandibular and sublingual glands in the neonatal rat.

Analysis of the soluble protein fractions from the rat parotid, submandibular and sublingual glands by polyacrylamide-gel electrophoresis reveals similarities in overall patterns of protein synthesis at birth. Tissue-specific changes in protein and glycoprotein synthesis occur shortly after birth and again at the time of weaning, 21--28 days later. Incorporation of [3H]thymidine into DNA was at its highest after birth and gradually decreased in both the parotid and submandibular gland, whereas [3H]thymidine incorporation in the sublingual gland was low throughout the time of neonatal development. [14C]Leucine incorporation into total protein increased in all glands with age after birth, showing an accelerated rate 21--28 days later. Trichloroacetic acid/phosphotungstic acid-precipitable [3H]fucose in glycoproteins declined over the time of neonatal development in the parotid and submandibular gland, but its incorporation remained higher in the sublingual gland. alpha-Amylase (EC 3.2.1.1) in the salivary glands increased at the time of weaning, as judged by detectability in sodium dodecyl sulphate/polyacrylamide gels and by immune precipitation. Two membrane-bound enzymes, UDP-galactose:2-acetamido-2-deoxy-D-glucosamine 4 beta-galactosyltransferase (EC 2.4.1.22) and UDP-galactose:2-acetamido-2-deoxy-D-galactosaminyl-protein 3 beta-galactosyltransferase (no EC number), undergo tissue-specific change rather than changes induced by physiological stimulation of the salivary glands.     

Collagen metabolism in the murine colon following X irradiation.

Female CBA mice, aged 16 weeks, were irradiated to the total pelvic region with either single doses (5-20 Gy) or two equal fractions (10- to 30-Gy total dose, 24-h interval) of 240 kV X rays. Total protein and collagen synthesis rates, collagen breakdown, and net collagen content of the colon were measured at various times postirradiation using a radioisotope incorporation method and HPLC analysis. Immunohistochemical staining and computerized image analysis were used to assess the relative amounts of collagen types I and III at various times postirradiation, in various regions of the colon. Total protein and collagen synthesis rates were elevated above control levels at 4 and 8 weeks postirradiation, as was collagen degradation. Values had returned to control levels by 16 weeks postirradiation, and there were no further changes up to 71 weeks postirradiation. The net amount of collagen in the colon did not change relative to controls at any time during the investigation. There was, however, increased immunohistochemical staining for collagen type I 52 weeks postirradiation in all regions of the colon and decreased staining of type III in the circular muscle layer and villi. Altered ratios of these two collagen isotypes are consistent with changes in mechanical properties of the tissue.     

Prolonged increase in T-cell receptor (TCR) variant fractions of spleen T lymphocytes in pregnant mice after gamma irradiation

To investigate the relationship between the radiation-induced increase of T-cell receptor (TCR) defective variant fractions and physiological status such as pregnancy, C57BL/ 6N mice were irradiated with 3 Gy of gamma rays at various days of gestation, just before and just after pregnancy. While the highest level of variant fractions in spleen T lymphocytes appeared at 9 days postirradiation and resolved fairly rapidly for nonpregnant mice, the increased variant fractions for pregnant mice irradiated at 16.5 days of gestation reached a plateau at 14 days postirradiation and remained at high levels until 28 days after irradiation. Therefore, variant fractions 28 days postirradiation were measured to determine the overall effect of radiation on the kinetics of TCR variant fractions during gestation. There was no significant difference in the baseline TCR variant fraction between unirradiated nonpregnant and pregnant mice. TCR variant fractions after irradiation were about twofold higher in pregnant mice (from 10.5 days of gestation until delivery) than those in nonpregnant mice. Both gamma radiation and pregnancy caused a decrease in the proportion of na?ve T-cell subsets and an increase in TCR variant fractions of na?ve T cells. In addition, the prolonged postirradiation increase in the TCR variant fractions of pregnant mice was associated with an increase in serum progesterone level. Differences between pregnant and nonpregnant mice in the kinetics of postirradiation restoration of T-cell systems may be involved in producing the differences in residual TCR variant fractions of these mice.     

Plasminogen activator activity in lung and alveolar macrophages of rats exposed to graded single doses of gamma rays to the right hemithorax

Male rats were sacrificed 2 or 6 months after a single dose of 0-30 Gy of 60Co gamma rays to the right hemithorax. At autopsy, macrophages were lavaged from the right lung, counted, and frozen. The right (irradiated) and the left (shielded) lungs were frozen, then assayed for plasminogen activator (PLA) activity by the fibrin plate lysis method. Freeze-thawed macrophages were assayed for both PLA activity (125I-fibrin clot lysis method) and fibrinolytic inhibitor activity (inhibition of urokinase-induced fibrin lysis). There was a linear, dose-dependent decrease in right lung PLA activity over the dose range of 10-30 Gy at 2 and 6 months postirradiation, reductions of 3.1 and 2.6% per Gy, respectively. PLA activity at all radiation doses was 10-15% higher at 6 months than at 2 months (P less than 0.05), indicative of a partial recovery of this endothelial function in the irradiated lung. There were no significant changes in PLA activity in the shielded left lung at any dose or time. There also was a linear, dose-dependent increase in the number of macrophages lavaged from the right lung at both 2 and 6 months postirradiation, with larger numbers recovered after all doses at 2 months. PLA activity per 10(6) macrophages decreased with increasing radiation dose at both autopsy times, closely paralleling lung PLA activity. This radiation-induced decrease in macrophage PLA activity was not due to increased fibrinolytic inhibitor activity in the irradiated macrophages. These data quantitate the dose response and time course of radiation-induced fibrinolytic defects in rat lung and suggest that information obtained from a minimally invasive procedure such as bronchoalveolar lavage may serve as an index of the degree of pulmonary fibrinolytic dysfunction after irradiation.     

Radiation-induced changes in collagen isotypes I, III, and IV in the lung of LAF1 mouse: effects of time, dose, and WR-2721

Alterations in the amount and distribution of pulmonary connective tissue are commonly observed subsequent to thoracic radiotherapy. The extent to which these changes are important in the expression of radiation damage and its repair remains unclear. We have quantitated changes in the parenchymal levels of collagen types I, III, and IV in the lungs of LAF1 mice at intervals to 1 year, following doses of 0-14 Gy, 300 kV X rays, or 0-18 Gy in the presence of the radioprotective compound, WR-2721. The method of quantitation, which involves video image analysis of fluorescent antibody stained, cryostat tissue sections, provides both quantitative and morphological information for the three collagen isotypes. Type I collagen peaked in tissue content at 15 and 30 weeks postirradiation (p.i.), with transient return to control values 20-25 weeks p.i. Type III collagen peaked at 15 and 25 weeks p.i. and declined in tissue content at 20 and 30 weeks. Type IV peaked 15-20 weeks following irradiation, returned to control levels at 25 weeks, and reached a plateau above control values after 30 weeks. Fluctuations in collagen levels in the parenchyma were dose dependent but were not simultaneous, indicating a radiation response characterized by alpha-chain-specific regulation of collagen biosynthesis and breakdown. In general, WR-2721, which enhanced postirradiation survival (DMF, 1.3), reduced the magnitude and altered the timing of collagen fluctuations; again, the effects were type specific. The results clearly demonstrate that the postirradiation response of the connective tissue is dose dependent, is specific to each macromolecule, and involves both deposition and removal of extracellular matrix. These processes are independently influenced by the presence during irradiation of WR-2721.     

Decreased saliva secretion and down-regulation of AQP5 in submandibular gland in irradiated rats

The molecular mechanisms of radiation-induced xerostomia remain unclear. The purpose of this study was to investigate the alterations of aquaporins (AQPs) and Na(+)/K(+)-ATPase in irradiated rat submandibular glands and to test the hypothesis that down-regulation of AQP5 expression in irradiated salivary glands is one of the mechanisms of radiation-induced xerostomia. Saliva from control and irradiated rat submandibular glands was analyzed. The mRNA level of AQP5 in the submandibular glands was assessed by semi-quantitative RT-PCR and in situ hybridization. The protein expression of AQP5, AQP1 and Na(+)/K(+)-ATPase was determined by Western blotting and immunohistochemistry. The body weight, submandibular gland weight, and saliva secretion of irradiated rats significantly decreased by 12, 24 and 32% on day 3 and 24, 16 and 38% on day 30 postirradiation, respectively. There was a significant increase in the protein concentration and osmolality of saliva in irradiated rats on days 3 and 30 postirradiation. However, there was no significant difference between irradiated and control rats in total saliva protein secretion. RT-PCR analysis showed that mRNA expression of AQP5 was significantly down-regulated by 37 and 51% in irradiated rats on days 3 and 30 postirradiation, respectively. Immunoblotting showed that the AQP5 protein level was decreased by 40 and 60% in irradiated glands, in contrast to the slight reductions of AQP1 and Na(+)/K(+)-ATPase proteins. Immunohistochemical analysis demonstrated that loss of AQP5 protein occurred throughout the irradiated glands, while no significant reduction was detected in AQP1 and Na(+)/ K(+)-ATPase labeling density. These results suggest that the preferential down-regulation of AQP5 with minor effects on AQP1 and Na(+)/K(+)-ATPase may contribute to radiation-induced salivary dysfunction.     

不同剂量的X-射线全身照射对小鼠健康状况及涎腺的影响

目的:通过直线加速器全身照射昆明小鼠建立辐射损伤模型,探索不同放射剂量对小鼠健康状况及涎腺功能和结构的影响。方法:选取八种不同剂量对昆明小鼠行体外全身照射,于照射后一个月内观察小鼠生长情况、体重变化;照射后一周、一个月检测各组小鼠血象的变化;测定放射半数致死剂量;照射后两个月,测定各组小鼠的唾液流量及唾液淀粉酶含量,并对下颌下腺组织切片行HE染色。结果:13Gy和15Gy照射组小鼠的体重逐渐下降,一周后死亡,其余组小鼠体重最终呈增加趋势。X-射线全身照射的半数致死量为10Gy。照射后一周,照射组小鼠的白细胞数目明显降低,与对照组比较有明显统计学差异(P0.01);在其他血象方面,除了7Gy组外,其他照射组与对照组比较也均有统计学差异(P0.05)。照射一个月后,各照射组小鼠的血象均恢复正常。照射后两个月,9Gy组和11Gy组小鼠的唾液流量及唾液淀粉酶含量均显著低于0Gy组,且11Gy组较9Gy组亦明显降低,差异均有统计学意义(P0.05)。随照射剂量的增加,小鼠的下颌下腺腺泡细胞数目逐步减少,结构排列紊乱,组织损伤逐渐加重。结论:X-射线全身照射引起小鼠健康状况受损,免疫功能减低,损伤程度与放射线强度呈剂量依赖性,小鼠半数致死量为10Gy,该剂量适合建立全身放射损伤模型。     

Evidence for reduced capacity for damage accumulation and repair in plateau-phase C3H 10T1/2 cells following multiple-dose irradiation with gamma rays

The effects of multiple-dose gamma irradiation on the shape of survival curves were studied with mouse C3H 10T1/2 cells maintained in contact-inhibited plateau phase. The dose-fractionation intervals included 3, 6, and 24 h. Following three fractionated doses (5 Gy per dose) of exposures, cells responded to further irradiation by displaying a survival curve with a much reduced shoulder width (Dq) compared to that of the survival curve measured in cells irradiated with single-graded doses alone. The effect on the mean lethal dose (D0) was small and appeared to be significant. The effect on reduction of Dq could not be completely overcome by lengthening the fractionation intervals from 3 to 6 h or 24 h, times in which repair of sublethal damage (SLD) measured by simple split-dose scheme and potentially lethal damage (PLD) measured by postirradiation incubation was completed. Other experiments showed that pretreatments of cells with fractionated irradiation appeared to slow down the cellular repair processes of SLD and PLD. Therefore, the observed change in the shape of survival curves after fractionation treatments may be attributed to a reduction of the cells' capacity for damage accumulation by an enhancement of the lethal expression of SLD and PLD. Although the molecular mechanism(s) is not known, the results of this study indicate that the acute graded dose-survival curve cannot be used a priori to extrapolate and reliably predict results of hyperfractionation. It is probable that for a nondividing or slowly dividing cell population, such an extrapolation may lead to an underestimation of cell killing. Furthermore, the findings of this investigation appear to support an interpretation, alternative to the high-linear energy transfer (LET) track-end postulate, for the effects on cell survival seen at low doses or low dose rates.     

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.