Modification of radiation damage in the canine kidney by hyperthermia: a histologic and functional study

The purpose of this study was to evaluate the effect of hyperthermia on the histologic and functional response of the canine kidney, a late-responding normal tissue, to irradiation. Both kidneys were irradiated. Radiation was delivered in single doses of 0, 10, or 15 Gy. Whole-body hyperthermia was used to produce renal kidney temperatures approximating 42.0 degrees C for 60 min. Thirty-six beagles were placed randomly in the following six treatment groups: control, whole-body hyperthermia alone, 10 Gy alone, 10 Gy + whole-body hyperthermia, 15 Gy alone, and 15 Gy + whole-body hyperthermia. Renal histologic and functional changes were assessed at 1 to 9 months after therapy. No changes were seen in glomerular filtration rate or renal tissue volumes in control or hyperthermia alone groups. Renal vascular and glomerular volumes were not affected significantly by any combination of hyperthermia and/or radiation. In all groups receiving radiation, glomerular filtration rate decreased, percentage renal tubular volume decreased, and interstitial volume increased significantly after therapy. The magnitude of these changes in the functional and histologic response of the kidney and the latent period before expression of this damage were dependent on radiation dose. However, hyperthermia did not modify expression of radiation damage in the kidney based on glomerular filtration rate and histologic quantification of renal tissue components.     

Reirradiation at long time intervals in mouse kidney: a comparison between experimental results and the predictions of the F-type tissue model

The tolerance of a late-responding tissue to reirradiation after long time intervals has been analysed using the F-type tissue model. In this model the tissue is composed of identical cells, each of which is capable of extensive proliferation and of tissue-specific function. The model was adapted to calculate the response to two fractions of radiation given in a variable overall time. For two equal doses of radiation the repair of tissue damage after the first fraction could be detected theoretically by a change in the rate of cell depletion after retreatment and by an increase in the minimum cell number attained. For an 'experimental set-up', in which a constant first dose was followed by a range of retreatment doses in a variable overall time, the repair of tissue damage theoretically could be detected most sensitively by a shift of the dose-response curves to higher retreatment doses as the time interval between the two doses was increased. A prerequisite for a proper comparison of these dose-response curves was that the responses were evaluated at times after the first dose determined by the minimal latency times after high retreatment doses. From a comparison of these theoretical results with experimental findings for mouse kidneys it was concluded that no recovery of tissue function took place over a 6-month period. Instead it appeared that the kidneys had become more sensitive to irradiation over this period.     

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。     

Cell proliferation and abnormal nuclei induced by radiation in renal tubule epithelium as an early manifestation of late damage

The time of appearance and the dose response of radiation effects in the mouse kidney were assessed from the determination of increases in labeling index, the appearance of proximal tubule cells with abnormally large nuclei, and kidney weight loss. Increased labeling indices and abnormally large nuclei were observed in the irradiated proximal tubule cells before any other histological changes were seen. The labeling index increased with dose (from 3 to 15 Gy) but not with time (from 1 to 12 months after irradiation). Increased labeling was evident as soon as 1 month after irradiation. Cell depletion as measured by a decrease in kidney weights compared to those of age-matched controls was not significant until 6 or more months after 11-, 13-, or 15-Gy irradiation. The frequency of cells with large nuclei increased steadily during the first 9 months after 15 Gy and tended to decline between 9 and 12 months, coincident with accelerating renal weight loss. These findings are consistent with the hypothesis that the production of these cells is a result of an abortive mitotic division and their loss is an eventual result of such an aberration. The increased proliferation induced by irradiation increases the chance for an abortive mitosis and death, presumably at a subsequent mitosis, of radiation-damaged proximal tubule cells, which is a major factor in the appearance of late radiation damage in the kidney.     

Radiation-induced renal damage: the effects of hyperfractionation

The response of mouse kidneys to multifraction irradiation was assessed using three nondestructive functional end points. A series of schedules was investigated giving 1, 2, 4, 8, 16, 32, or 64 equal X-ray doses, using doses per fraction in the range of 0.9 to 16 Gy. The overall treatment time was kept constant at 3 weeks. Kidney function was assessed from 19 to 48 weeks after irradiation by measuring changes in isotope clearance, urine output, and hematocrit. The degree of anemia (assessed from the hematocrit measurements) is a newly developed assay which is an early indicator of the extent of renal damage after irradiation. All three assays yielded steep dose-effect curves from which the repair capacity of kidney could be estimated by comparing the isoeffective doses in different schedules. There was a marked influence of fractionation, with increasing dose being required to achieve the same level of damage for increasing fraction number, even between 32 and 64 fractions. The data are well fitted by a linear quadratic dose-response equation, and analysis of the data in this way yields low values (approximately 3.0 Gy) for the ratio alpha/beta. This would suggest that hyperfractionation , using extremely small X-ray doses per fraction, would spare kidneys relative to tumors and acutely responding tissues.     

The kinetics of repair in mouse lung after fractionated irradiation

The kinetics of repair of sublethal damage in mouse lung was studied after fractionated doses of 137Cs gamma-rays. A wide range of doses per fraction (1.7-12 Gy) was given with interfraction intervals ranging from 0.5 to 24 h. The data were analysed by a direct method of analysis using the incomplete repair model. The half-time of repair (T1/2) was 0.76 h for the pneumonitis phase of damage (up to 8 months) and 0.65 h for the later phase of damage up to 12 months. The rate of repair was dependent on fraction size for both phases of lung damage and was faster after large dose fractions than after small fractions. The T1/2 was 0.6 h (95 per cent c.1. 0.53, 0.69) for doses per fraction greater than 5 Gy and 0.83 h (95 per cent c.1 0.76, 0.92) for doses per fraction of 2 Gy. Repair was nearly complete by 6 h, at least for the pneumonitis phase of damage. To the extent that extrapolation of these data to humans may be valid, these results imply that treatments with multiple fractions per day that involve the lung will not be limited by the necessity for interfraction intervals much longer than 6 h.     

Hypertension after bilateral kidney irradiation in young and adult rats

The mechanism of a rise in blood pressure after kidney irradiation is unclear but most likely of renal origin. We have investigated the role of the renin-angiotensin system and dietary salt restriction in the development of systolic hypertension after bilateral kidney irradiation in young and adult rats. Three to 12 months after a single X-ray dose of 7.5 or 12.5 Gy to both kidneys of young and adult rats, the systolic blood pressure (SBP) and plasma renin concentration (PRC) were measured regularly. A single X-ray dose of 12.5 Gy caused a moderate rise in SBP and a slight reduction in PRC in both young and adult rats. A dose of 7.5 Gy did not significantly alter the SBP or PRC during the follow-up period of 1 year. In a second experiment, the kidneys of young rats received an X-ray dose of 20 Gy. Subsequently, rats were kept on a standard diet (110 mmol sodium/kg) or a sodium-poor diet (10 mmol sodium/kg). On both diets, SBP started to rise rapidly 3 months after kidney irradiation. Sodium balance studies carried out at that time revealed an increased sodium retention in the irradiated rats compared to controls on the same diet. In rats on a low sodium intake, there was neither a delay nor an alleviation in the development of hypertension. Compared to controls, the PRC tended to be lower in irradiated rats up to 4 months after irradiation. Subsequently, malignant hypertension developed in all 20 Gy rats, resulting in pressure natriuresis, stimulating the renin-angiotensin system. Our findings indicated that hypertension after bilateral kidney irradiation was not primarily the result of an activation of the renin-angiotensin system. Although there were some indications that sodium retention played a role, dietary sodium restriction did not influence the development of hypertension.     

Radioprotective effect of hypoxic hypoxia (8% O2) for different morphological elements of mouse kidney

The breathing of gas mixtures containing 8-9% O2 during irradiation of tumors has been tested at several cancer clinics (in Russia and abroad) with the purpose of decreasing the morbidity of normal issues, thus providing the possibility to increase the dose of radiation. Previous experiments have demonstrated a broad spectrum of dose modification factors (DMF) for different normal tissues as well as for different transplanted tumors, with in general larger protection of normal tissues. The present study was designed to assess the radioprotective effect for mouse kidney of breathing a gas mixture containing 8% O2 by morphometry of histological specimens. Both kidneys were locally irradiated using single fractions (11-19 Gy in air and 13-19 Gy in hypoxia) or 5 fractions separated by 24 h intervals (25-35 Gy in air and 30-40 Gy in hypoxia). Histological examination was performed 8 and 10 months after treatment. The DMF for glomeruli damage (glomerulosclerosis, ecstatic capillaries, hemorrhage) was in the range 1.25-1.29. Tubular damage showed a DMF of 1.28-1.37. Using the endpoint of development of interstitial tissue in the cortex a DMF of 1.32-1.37 was found after a single treatment, and 1.48 after fractionated irradiation. The radioprotective effect for arteriolar lesions was lower than measured using the above endpoints, namely 1.13-1.15 after single and 1.16-1.18 after fractionated irradiation. It was shown previously on groups of animals treated in the same manner that the DMF was between 1.24-1.26 when renal damage was assessed by hematocrit measurements, between 1.32-1.28 when it was evaluated by urination frequency, and 1.23-1.27 when kidney wet and dry weights were used as end-points. All these data witness that breathing 8% oxygen increases the tolerance of kidney function with a DMF above 1.2. The impact of low protection of arterioli on renal function in the late period after radiotherapy needs additional study.     

Effects of split-dose X irradiation on rat salivary gland function.

The effect of a single local dose of 15 Gy on salivary gland function in male Albino Wistar rats was compared with the effect of two doses of 7.5 Gy. The intervals chosen were 0-24 h and 1 week. Before and 1-30 days after the last radiation dose, samples of parotid and submandibular saliva were collected simultaneously after stimulation of the glands with pilocarpine. Irradiation with the single dose resulted in an increased lag phase and potassium concentration, and a decreased flow rate and sodium concentration. The rate of secretion of amylase was decreased during Days 1-6, increased at Day 10, and was decreased again at Day 30. With two dose fractions, substantial dose-sparing effects on lag phase, flow rate, and secretion of amylase were observed for both the very early (0-6 days postirradiation) and later (6-30 days postirradiation) effects. These effects were maximal when the interval between the fractions was 6 h. A significant dose-sparing effect on electrolytes was observed for the later effects only, again with a maximum for the 6-h interval. The dose-sparing observed for the very early effects cannot be explained satisfactorily by repair of sublethal damage (SLD), redistribution of cells over the cell cycle, or repopulation of salivary gland tissue between the doses. In contrast to the earlier dose-sparing effects, the split-dose recovery seen for later damage may be attributed, in part, to SLD repair in providing for greater reproductive survival of intercalated ductal cells and enhanced tissue regeneration.     

CFU-S and haematopoietic microenvironment in mice after fractionated irradiation. A study on spleen colonies.

The paper is aimed at evaluating the quantity and quality of the haematopoietic stem cells, CFU-S, in the bone marrow and the functional effectiveness of the haematopoietic microenvironment of the spleen in two time intervals after repeated exposure of mice to doses of 0.5 Gy gamma-rays once a week (total doses of 12 and 24 Gy). After irradiation, bone marrow was cross-transplanted between fractionatedly irradiated and control mice. The parameter evaluated were numbers of spleen colonies classified into size categories. The data obtained provide evidence for a significant damage to the CFU-S, concerning both their number and proliferation ability, after both total doses used. The functional effectiveness of the haematopoietic microenvironment of the spleen was impaired only in bone marrow recipients receiving a transplant after having been exposed to a total dose of 24 Gy; this dose combined with subsequent pre-transplantation irradiation resulted in a marked suppression of cell production within the spleen colonies formed from a normal bone marrow on the spleens of fractionatedly irradiated mice.     

Use of Pulsed Low–Dose Rate Radiotherapy in Refractory Malignancies

BACKGROUND: Most tumor cell lines exhibited low-dose hyperradiosensitivity (LDHRS) to radiation doses lower than 0.3 Gy. Pulsed low–dose rate radiotherapy (PLDR) took advantage of LDHRS and maximized the tumor control process. In this study, we retrospectively analyzed patients receiving PLDR for refractory malignancies. PATIENTS AND METHODS: In total, 22 patients were included in our study: 9 females and 13 males. The median age was 61 years old. All the patients previously received multiline treatments and failed with an estimated survival less than 6 months. Thus, palliative PLDR was given. The PLDR was delivered using 10 fractions of 2 Gy/day, with an interval of 3 minutes, for 5 days per week. The dose rate was 6.67 cGy/min. The median follow-up was 1 year (range 8-30 months). Nine patients underwent PLDR for reirradiation due to locally recurrent diseases. The time interval from last irradiation was 11 to 168 months. Ten patients received PLDR due to poor performance status. Three patients were given PLDR for bulky tumor. The irradiated sites included primary disease (seven patients), locally recurrent disease (nine patients), and retroperitoneal adenopathy (six patients). RESULTS: Five patients developed grade 3 or 4 toxicities. No grade 5 toxicities occurred. All the toxicities recovered after treatments. In general, the 1-year local-regional control rate was approximately 40%, and almost all the patients developed progression at the second year after PLDR. The 6-month survival rate was 76%, and the 1-year survival rate was 69%. For the three patients given PLDR for bulky tumor, all of them achieved partial remission 1 month after the PLDR, and one patient achieved complete response at the fourth month. CONCLUSION: PLDR is an effective and safe option not only for reirradiation but also for patients with poor performance status or bulky tumors. A prospective clinical trial (NCT03061162) is ongoing to validate our results.     

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.     

A test of equal effect per fraction in the kidney of the mouse.

Measurements of renal damage in the mouse were made to determine if there was an equal effect per fraction during a course of repeated 240-kVp X-ray doses. An X-ray dose of 2 Gy was given 2, 8, 14, or 20 times with interfraction intervals of 12 h. Some animals were also irradiated with twenty 2-Gy doses using a 5-h interfraction interval. The underlying effect per fraction (-logeSF of the notional target cell population) was determined from the additional top-up dose of d(4)-Be neutrons needed to produce measurable renal impairment assessed by decreased clearance from the plasma of [51Cr]EDTA and by a reduction in the hematocrit at 25, 29, 33, and 39 weeks after treatment. There was no significant influence of the time of assay on the values of underlying effect measured. A mean value of underlying effect was therefore calculated for the two different assays of each mouse, from the measurements at the four times. This gave approximately 40 estimates (one for each animal assessed) with each assay of the effectiveness of 2-Gy fractions in each of the four fractionation schedules, a total of 321 determinations in the study with 12-h intervals. Regression analysis showed that there was no significant trend in underlying effect per fraction with number of fractions, i.e., the damage per fraction was constant regardless of the number of fractions used. With underlying effect normalized to 1 unit of damage for a single 2-Gy dose, the slope of this plot was -0.0013 per fraction2 +/- 0.0097 (95% CL). The assumption of equal effect per fraction was therefore not invalidated in the kidney of the mouse. With a 5- instead of a 12-h interfraction interval, the 20-fraction schedule was 7% more effective as measured by the two assays analyzed together; this was significant at P = 0.0001. This shows that 5 h is not sufficient time between fractions for full repair to occur in the kidney, and underlines the need for intervals of at least 6 h between the doses in clinical radiotherapy using more than one fraction per day. The data are consistent with an alpha/beta ratio approximately 1.6 Gy, with a repair half-time approximately 1.3 h. However, these experiments were not designed to determine these parameters and their values should be regarded only as rough estimates.     

Sexual Dimorphism in Development of Kidney Damage in Aging Fischer-344 Rats

BackgroundAging kidneys exhibit slowly developing injury and women are usually protected compared with men, in association with maintained renal nitric oxide.ObjectivesOur purpose was to test 2 hypotheses: (1) that aging intact Fischer-344 (F344) female rats exhibit less glomerular damage than similarly aged males, and (2) that loss of female ovarian hormones would lead to greater structural injury and dysregulation of the nitric oxide synthase (NOS) system in aging F344 rat kidneys.MethodsWe compared renal injury in F344 rats in intact, ovariectomized, and ovariectomized with estrogen replaced young (6 month) and old (24 month) female rats with young and old intact male rats and measured renal protein abundance of NOS isoforms and oxidative stress.ResultsThere was no difference in age-dependent glomerular damage between young or old intact male and female F344 rats, and neither ovariectomy nor estrogen replacement affected renal injury; however, tubulointerstitial injury was greater in old males than in old females. These data suggest that ovarian hormones do not influence these aspects of kidney aging in F344 rats and that the greater tubulointerstitial injury is caused by male sex. Old males had greater kidney cortex NOS3 abundance than females, and NOS1 abundance (alpha and beta isoforms) was increased in old males compared with both young males and old females. NOS abundance was preserved with age in intact females, ovariectomy did not reduce NOS1 or NOS3 protein abundance, and estrogen replacement did not uniformly elevate NOS proteins, suggesting that estrogens are not primary regulators of renal NOS abundance in this strain. Nicotinamide adenine dinucleotide phosphate oxidase-dependent superoxide production and nitrotyrosine immunoreactivity were increased in aging male rat kidneys compared with females, which could compromise renal nitric oxide production and/or bioavailability.ConclusionsThe kidney damage expressed in aging F344 rats is fairly mild and is not related to loss of renal cortex NOS3 or NOS1 alpha.     

Correlation between the duration of radiation adaptive response in bone marrow cells of mice and the dose of gamma-irradiation in vivo

The dependence between the adaptive response and adaptive dose was studied on the basis of cytogenetic damage in polychromatic erythrocytes of bone marrow cells in mice after a low dose gamma-irradiation in vivo. The adaptive response to doses of 0.1 and 0.2 Gy was found to be retained for at least two months after irradiation. However, the adaptive dose of 0.4 Gy did not induce prolonged adaptive response.     

Kidney and lung injury in irradiated rats protected from acute death by partial-body shielding

Ninety-six CD-1 male rats were exposed to gamma-ray doses (0-25 Gy) in increments of 5 Gy. One femur, the surgically exteriorized GI tract, and the oral cavity were shielded during irradiation to protect against acute mortality from injury to the hematopoietic system, small intestine, and oral cavity. In addition, the thoraxes of half of the animals from each dose group were shielded. At approximately monthly intervals from 2 to 10 months after irradiation the hematocrit, plasma urea nitrogen (PUN), and 51Cr-EDTA clearance were measured. During the study 20 thorax-shielded and 19 thorax-irradiated animals died. All rats whose thoraxes received 25 Gy irradiation and three out of seven rats whose thoraxes received 20 Gy died 1 to 3 months postirradiation with massive pleural fluid accumulation. Shielding the thoraxes prevented this mode of death at these doses. Kidney injury was judged to be the primary cause of death of all thorax-shielded animals and 15- and 20-Gy thorax-irradiated animals. Animals with kidney damage had elevated PUN and reduced 51Cr-EDTA clearance and hematocrits. The relative merits of each of these end points in assessing radiation-induced kidney injury after total-body exposure are discussed.     

Low doses of radiation decrease the level of spontaneous and gamma-induced chromosomal mutagenesis in bone marrow cells of mice in vivo

Low doses of ionizing radiation are known to induce adaptive response (AR), which is characterized in most cases by temporary nature, though the possibility of long-term persistence of AR is not ruled out. In this investigation we studied the effect of low doses of gamma-radiation on both high-dose radiation-induced and spontaneous level of cytogenetic damage throughout the life of mice. SHK male mice 2 months old were used. Priming doses of 0.1 and 0.2 Gy (0.125 Gy/min, gamma-radiation from 60Co) were used. A challenging dose of 1.5 Gy (1 Gy/min) was used in the experiments using a routine AR experimental design. The frequency of micronucleated polychromatic erythrocytes in bone marrow cells of primed, primed and challenged, and control groups was assessed at various times of animal life span. It was shown that: a) single low-dose gamma-irradiation induces a cytogenetic AR which can be revealed at 1, 3, 6, 9, 12 months after priming; b) single low-dose gamma-irradiation decreases the cytogenetic damage to a level below the spontaneous rate at the end of lifetime (20 months) of animals; c) ability to induce adaptive response does not depend on the age of animals at the moment of priming irradiation. In conclusion, the mechanisms underlying AR not only protect from chromosome damage induced by high-dose irradiation but also may play a role in spontaneous mutagenesis during aging of animals.     

The recovery of humoral immunity after the long-term action of tritium oxide at different irradiation levels

Dynamics of recovery of humoral immunity of CBA mice was studied 1, 3, 6 and 12 months after termination of long-term exposure to tritium oxide at various levels of absorbed doses (3, 5 and 9 Gy) and dose rates (3.3, 4.9 and 9.2 cGy.day-1). A severer and more stable residual radiation damage was observed in the department of lymphocyte precursors. A considerable decrease in the content of antibody producers was due to the lymphoid tissue hypoplasia. There was a direct relationship between the immunodeficiency and dose rate and total absorbed dose of beta radiation.     

全氟辛烷磺酸钾对小鼠肾脏的氧化性损伤

目的:以小鼠肾脏细胞中的活性氧(ROS)、丙二醛(MDA)、谷胱甘肽(GSH)含量和超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)活力为指标,探讨全氟辛烷磺酸钾(PFOS-K)对小鼠肾脏的氧化性损伤作用。方法:以剂量为6mg/kg·bw、12 mg/kg·bw、24 mg/kg·bw 3个浓度的PFOS-K混悬液,每天分别给小鼠经口灌胃一次,连续染毒20天后检测肾脏脏器系数,以及肾脏中ROS、MDA、GSH含量的变化和SOD、GSH-Px、CAT活性的改变。结果:与阴性对照组相比,在6-24 mg/kg·bw剂量范围内,PFOS-K使小鼠体重下降、肾脏重量增加、肾脏脏器系数增大,且表现出一定的剂量-效应关系(r小鼠体重=-0.905,r肾脏湿重=0.938,r脏器系数=0.936)。PFOS-K使小鼠肾脏内活性氧(ROS)及丙二醛(MDA)含量增多(rROS=0.990,rMDA=0.997)、谷胱甘肽(GSH)含量减少(rGSH=-0.994),超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)活力降低(rSOD=-0.917,rGSH-Px=-0.986,rCAT=-0.991)。结论:本试验条件下,PFOS-K致使小鼠肾脏肿大,影响了肾脏的发育;造成了肾脏的氧化性损伤,肾组织内抗氧化酶系统遭到破坏,氧化应激反应增强,具有氧化损伤作用。