维生素D对不同剂量X射线照射小鼠免疫功能的保护作用

目的 观察维生素D对不同剂量X射线照射小鼠免疫功能的影响。方法 将小鼠采用随机数字表法分为5组:健康对照组、2 Gy和5 Gy照射组、2 Gy+药物(维生素D)组和5 Gy+药物(维生素D)组。给药组小鼠在不同剂量X射线照射后,连续7 d腹腔注射6 IU维生素D[1,25(OH)₂D₃]/g体重,于给药后第8天,5组小鼠均处死。测定小鼠体重、胸腺和脾脏指数,ConA诱导的脾脏T淋巴细胞增殖能力,ELISA法检测脾细胞IL-2的分泌量。结果 与健康对照组相比,2和5 Gy照射组小鼠脾脏T淋巴细胞增殖能力、脾细胞IL-2的分泌量均显著降低(F=36.20、7.13,P<0.05);与2 Gy照射组相比,2 Gy+药物组小鼠胸腺指数、脾脏指数、脾脏T淋巴细胞增殖能力均显著增高(t=-2.54、-2.24、-2.84,P<0.05);与5 Gy照射组相比,5 Gy+药物组小鼠的胸腺指数、脾细胞IL-2的分泌量显著增高(t=-5.02、-2.64,P<0.05)。结论 维生素D能够改善受照小鼠的免疫功能,但随照射剂量增大,改善作用减弱。     

肌肽对小鼠放射性肺损伤的防治作用

目的 了解肌肽对小鼠放射性肺损伤的防治作用。方法 近交系C57/BL 雌性小鼠108只,随机数字表法分为对照组、单纯照射组、照射+肌肽组（15 mg·kg^-1·d^-1）和单纯肌肽组（15 mg·kg^-1·d^-1）,对照组共18只,其他各组每组30只。采用10 MV X射线经前胸单次照射小鼠肺脏中平面13 Gy,全肺照射。两肌肽组灌胃给予15 mg·kg^-1·d^-1肌肽,照射前30 min给药1次,以后1 次/d至实验结束,对照组给予相应同体积生理盐水。在照射后7、28和56 d处死后取部分肺组织HE染色,部分肺组织行超氧化物歧化酶（SOD）检测,同时ELISA法测定血清中TGF-β1、TNF-α。结果 受照射组（单纯照射组、照射+肌肽组）在照射后56 d均表现出不同程度的放射性肺炎病理变化,照射+给药组较单纯照射组炎症反应明显较轻。各组间不同时段血清中TGF-β1水平差异有统计学意义（F=10.65、3.70、4.04,P<0.05）;各组间不同时段血清中TNF-α水平差异有统计学意义（F=39.55、53.38、4.01,P<0.05）;各组间不同时段肺组织中SOD水平差异有统计学意义（F=4.33、4.19、3.34,P<0.05）。照射+肌肽组较同期的单纯照射组,肺组织中SOD水平明显较高,血清中TGF-β1、TNF-α 明显降低。结论 肌肽通过保护SOD,降低TGF-β1和TNF-α水平起到预防并减轻小鼠放射性肺损伤的作用。     

吡格列酮对大鼠放射性心肌纤维化的防治作用

目的 探究吡格列酮是否能减轻大鼠放射性心肌纤维化。方法 46只Sprague-Dawley(SD)大鼠按随机数字表法分成6组(对照组、吡格列酮10 mg ·kg^-1 ·d^-1组、吡格列酮20 mg ·kg^-1 ·d^-1组、18 Gy照射+安慰剂组、18 Gy照射+吡格列酮10 mg ·kg^-1 ·d^-1及18 Gy照射+吡格列酮20 mg ·kg^-1 ·d^-1组)。X射线局部照射大鼠心脏后,予以吡格列酮或者安慰剂1个月。3个月后,取心脏组织马松染色,观察心肌纤维化程度;Western blot分析各组蛋白表达程度;Real-time PCR观察各组过氧化物酶体增生物激活受体-γ(PPAR-γ)mRNA的表达。结果 马松染色示暴露于射线的大鼠心肌有明显纤维化,同时给予吡格列酮的大鼠心肌纤维化不明显。Western blot分析示PPAR-γ蛋白在照射组心脏的表达高于非照射组(F=12.435, P<0.05),照射+安慰剂组的转化生长因子-β1 (TGF-β1)蛋白表达高于其余5组(F=17.578,P<0.05),细胞周期蛋白依赖激酶5 (CDK5)蛋白在3个照射组的蛋白表达较高,但仅在照射+安慰剂组的升高差异有统计学意义(F=3.651,P<0.05)。Real-time PCR示PPAR-γ mRNA 在照射+吡格列酮20 mg ·kg^-1 ·d^-1组的表达高于吡格列酮20 mg ·kg^-1 ·d^-1组(F=2.333,P<0.05)。结论 吡格列酮通过其抗纤维化活性可减少大鼠放射性心肌纤维化,可能是通过抑制CDK5介导的PPAR-γ磷酸化而发挥作用。     

阿魏酸对小鼠骨髓造血功能辐射损伤的防护作用

目的 观察阿魏酸对小鼠外周血象和骨髓造血功能辐射损伤的防护作用,初步探讨阿魏酸的抗辐射作用机制。方法 6~8周ICR小鼠96只,随机数表法分为正常对照组、照射模型组、阳性药（408片）治疗组和阿魏酸10、30、90 mg ·kg^-1·d^-1治疗组,每组16只。小鼠初次给药后24 h接受3.5 Gy ⁶⁰Co γ单次全身照射,之后连续7 d给药。其中,每组10只用于观察照射前2 d及照射后3、7、10、15、22 d的外周血象;其余6只用于照射后7 d检测骨髓嗜多染红细胞的微核细胞率、造血祖细胞集落形成能力、以及Thbd和HMGB1蛋白的表达水平。结果 与照射模型组比较,90 mg ·kg^-1 ·d^-1的阿魏酸可有效提高小鼠3.5 Gy照射后3、10、15、22 d的外周血白细胞数（t=2.267、2.399、1.945、2.828,P<0.05）,显著降低骨髓嗜多染红细胞微核细胞率（t=4.013,P<0.05）,明显提高造血祖细胞红细胞集落生成单位（CFU-E）、红细胞爆裂型集落生成单位（BFU-E）和粒-单细胞集落生成单位（CFU-GM）的集落形成能力（t=2.366、2.953、3.115,P<0.05）,并提高骨髓细胞中Thbd和核内HMGB1蛋白表达水平（t=17.75、23.39,P<0.01）。结论 阿魏酸可通过调节Thbd和HMGB1蛋白表达,促进小鼠骨髓造血功能辐射损伤修复,加速外周血象恢复。     

禁食对137Cs γ射线照射诱导小鼠肠道辐射损伤的代谢组学研究

目的 研究禁食对¹³⁷Cs γ射线照射诱导小鼠肠道辐射损伤的干预作用,通过非靶向代谢组学探究小鼠粪便代谢物的变化。方法 将小鼠分为健康对照组、γ射线照射（全身9 Gy或腹部15 Gy）组、禁食（24、48、72 h）+照射（全身9 Gy或腹部15 Gy）组。照射后,计算小鼠的生存率、脾脏指数和胸腺指数。非靶代谢实验测序分为4组,分别为健康对照组、禁食24 h组、腹部局部照射15 Gy组、禁食24 h组+腹部局部照射15 Gy组、每组6只。于照后3.5 d收集各组小鼠的粪便进行非靶向代谢组学检测。结果 9 Gy γ射线全身照射小鼠照射前禁食48和24 h,受照后的中位生存期提高了1和4 d;15 Gy腹部受照小鼠照射前禁食48和24 h的小鼠的存活率分别为16.67%和25%,照射前禁食24 h能够提高受照后3.5 d小鼠的体重（t=2.338,P=0.042）和脾脏指数（t=2.289,P=0.045）。非靶向代谢组学结果显示,禁食24 h和未禁食的受腹部局部照射小鼠粪便样本中有30个差异表达代谢物;代谢通路富集分析表明,类固醇激素生物合成的代谢途径存在着不平衡状态。结论 照射前禁食可以提高肠道辐射损伤小鼠的生存率,改变其肠道代谢产物,提示照射前禁食或短期内饮食营养变化参与调节肠道辐射损。     

低剂量辐射适应性反应对辐射诱发小鼠胸腺淋巴瘤的影响

目的 探讨低剂量辐射对致癌剂量辐射诱发小鼠胸腺淋巴瘤的影响及其免疫学机理。方法 采用4次1.75GyX射线全身照射C57BL/6J小鼠诱发胸腺淋巴瘤模型, 观察不同剂量照后6个月小鼠胸腺淋巴瘤发生率, 照后1个月脾脏NK细胞毒活性、IL-2和γIFN分泌活性、腹腔巨噬细胞吞噬功能及其TNFα分泌活性以及胸腺细胞分化的变化。结果 每次1.75Gy照射前6h或12h接受25mGy或75mGy全身照射均可降低胸腺淋巴瘤发生率, 且预先接受75mGy全身照射的作用效果更为明显; 每次1.75Gy照射前12h接受75mGy照射小鼠, 上述免疫指标均比单纯1.75Gy照射组增强, 且多数指标接近假照射组; 其胸腺CD4^-CD8^-和CD4^-CD8⁺细胞较单纯1.75Gy照射组减少、CD4⁺CD8⁺细胞增多。结论 低剂量辐射可诱导辐射诱发胸腺淋巴瘤适应性反应, 对致癌剂量辐射诱发小鼠胸腺淋巴瘤有抑制作用, 其抑制作用的免疫学机理可能与低剂量辐射的免疫增强效应及诱导的免疫学适应性反应, 减轻致癌剂量辐射对机体免疫功能的损伤, 使胸腺淋巴瘤前体细胞在形成胸腺淋巴瘤之前被免疫系统清除有关。     

不同剂量率60Co γ射线照射对人外周血辐射敏感基因表达变化的影响

目的 探讨不同剂量率⁶⁰Co γ射线照射对辐射诱导的基因表达水平改变的影响。方法 ⁶⁰Co γ射线照射3例正常人离体外周血,剂量率分别为0.2、1.0和2.0 Gy/min,照射剂量为0、1、2、4和6 Gy,照射后24 h收集细胞,实时荧光定量（PCR）法对11个基因（CDKN1A、MDM2、PCNA、FDXR、GADD45A、PHPT1、ASTN2、TNFSF4、POLH、GDF-15和PPM1D） mRNA表达水平进行相对定量检测;逐步回归法构建不同剂量率基因组合表达模型。结果 不同剂量率0.2、1和2 Gy/min ⁶⁰Co γ射线照射后,辐射诱导的11个基因的相对表达量随照射剂量增加而升高,具有显著的剂量依赖性（R²=0.744~0.998,P< 0.05）;0.2 Gy/min ⁶⁰Co γ射线照射2 Gy后,CDKN1A、FDXR、PHPT1和TNFSF4基因的表达量明显高于1和2 Gy/min剂量率组,差异具有统计学意义（t=3.73、5.73、2.44、2.77、3.53、2.68、2.43、2.05,P< 0.05）;2 Gy/min ⁶⁰Co γ射线照射6 Gy后,PPM1D基因表达量明显高于其他两个剂量率组（t=3.82、2.54,P< 0.05）;不同剂量率基因组合表达模型由2~3个基因组成,回归方程的R²值为0.951~0.976（P< 0.05）。结论 在0.2~2 Gy/min剂量率范围内,不同剂量率⁶⁰Co γ射线照射可能会影响辐射诱导人外周血基因表达水平的改变。     

正常肺组织大分割照射全肺平均耐受剂量与生物学效应研究

目的 建立正常组织分次照射基于肺纤维化影像学改变的全肺平均剂量-效应模型,定量分析分割照射相比单次照射的生物学效应及耐受剂量关系。方法 采用8~10周龄C57BL6雌性小鼠按随机数表法分组进行X射线全肺野照射,分别给予梯度剂量0、2.0 Gy×5次、4.0 Gy×5次、6.0 Gy×5次、7.0 Gy×5次、8.5 Gy×5次。照射后24周行CT扫描成像,CT图像三维重建后经三维分割算法获得肺部平均密度与肺部体积值,并分别据此进行Boltzmann模型放射生物学建模。结果 照射后24周CT图像三维重建冠状位图像提示剂量依赖的肺部影像学改变。同一时间点肺组织全基因组芯片与组织病理学研究均提示与影像学改变高度吻合。经放射生物学建模,分次照射诱导肺密度改变的全肺平均剂量（D_mean）中位剂量为（30.80±0.80）Gy（校正R²=0.97）;引起肺体积减小的中位剂量为（31.31±7.07）Gy（校正R²=0.92）。基于影像学参数的剂量-效应曲线提示,肺组织对分次照射的耐受性相比单次照射显著提高。结论 纤维化进展过程中,肺密度与肺体积改变对X射线的依赖性不仅取决于总剂量大小,也与分割次数、分次剂量存在一定关联。     

miR-424*在X射线照射后的A549细胞体内、外及非小细胞肺癌组织和血清中的表达

目的 研究2、4 Gy X射线照射后人肺腺癌细胞miR-424^*体内、外表达以及非小细胞肺癌患者肺组织及血清中miR-424^*的表达变化及其意义。方法 2、4 Gy X射线分别照射体外培养的A549细胞,以实时定量PCR（RT-qPCR）法检测A549细胞中miR-424^*表达水平;用照射后的A549细胞制备裸鼠肺转移动物模型,检测裸鼠肺组织及血清中miR-424^*的表达水平;收集肺癌患者肺组织及血清样本,检测miR-424^*表达水平。结果 2、4 Gy X射线照射后1、2、12、24及48 h,miR-424^*表达均显著升高（2 Gy：t=-45.886~-6.709,P<0.05;4 Gy：t=-29.087~-7.833,P<0.05）;0、2、4 Gy照射后,miR-424^*在裸鼠肺及血清中表达水平分别为空白对照组的9.72、8.58及4.7与11.93、9.22及8.99倍（t=-13.243~-3.052,P<0.05）。6/11例（54.5%）患者肺癌组织中高表达miR-424^*,腺癌、鳞癌病理类型间检出率差异无统计学意义（P>0.05）;43/84例（51.20%）肺癌患者与健康志愿者相比,血清miR-424^*表达升高 1.97~17.71倍,其中腺癌患者血清检出率为39.1%（18/46）,鳞癌患者血清检出率为65.8%（25/38）,两种病理类型检出率差异有统计学意义（t=5.919,P<0.05）;此外,84例肺癌患者中,miR-424^*[JP3]在未接受放疗的肺癌患者血清中的阳性检出率为41.5%（22/53）,显著低于接受放疗的肺癌患者血清的阳性检出率67.7%（21/31）[JP]（t=5.387,P<0.05）。结论 2、4 Gy X射线照射可增加A549细胞miRNA-424^*的体内、外表达水平,可能与增强A549细胞体内、外侵袭转移能力有关。肺癌患者中50%以上的肺癌组织及肺癌患者血清中miR-424^*表达水平显著升高,可能与肺癌的病理类型及放疗相关。     

穿心莲内酯对小鼠放射性肺损伤的防护作用

目的 观察穿心莲内酯对C57BL/6小鼠放射性肺损伤的保护效应。方法 将80只C57BL小鼠完全随机分为0.9% 氯化钠溶液组（空白对照组）、穿心莲内酯组（单纯给药组）、放射+0.9%氯化钠溶液组（单纯照射组）和放射+穿心莲内酯组（联合组）,每组20只。照射前单纯给药组和联合组用穿心莲内酯 20 mg·kg^-1·d^-1灌胃,空白对照组和单纯照射组用等体积0.9%氯化钠溶液灌胃,连续灌胃30 d。采用6 MV高能X射线直线加速器单次15 Gy照射,建立小鼠全肺放射性肺损伤模型。取小鼠肺组织HE染色、Masson染色进行组织病理学观察;采用 ELISA 法检测小鼠血清转化生长因子β1（TGF-β1）、肿瘤坏死因子α（TNF-α）;紫外分光光度计检测肺组织丙二醛（MDA）含量、超氧化物歧化酶（SOD）活力和羟脯氨酸（Hyp）含量。结果 联合组小鼠肺组织损伤程度较单纯照射组小鼠明显减轻,其肺系数、肺组织MDA含量、羟脯氨酸含量以及血清 TGF-β1、TNF-α表达水平虽然略高于空白对照组,但低于单纯照射组差异有统计学意义（t_肺系数=1,60, t_MDA=7.06, t_羟脯氨酸=17.44, t_TGF-β1=16.67, t _TNF-α=14.03,P <0.05）;联合组小鼠血清SOD活力明显高于单纯照射组（t=60.81,P<0.05）,但低于空白对照组和单纯给药组;单纯给药组小鼠各项检测指标与空白对照组相比,差异均无统计学意义。结论 穿心莲内酯可有效减轻小鼠的放射性肺损伤,且对小鼠肺组织无明显毒性。     

西咪替丁对胸部分割照射小鼠脾脏损伤的治疗作用

目的探究西咪替丁(CMTD)对局部分割照射小鼠的治疗作用。方法雄性C57BL/6小鼠30只,随机单位组设计分为对照组、单纯照射组和照射给药组(CMTD,100 mg/kg),每组10只;采用X射线局部分割照射小鼠右胸腔,8 Gy/d照射,连续3 d,累积照射剂量为24 Gy,剂量率为0.883 Gy/min。照射后连续7 d给予照射给药组小鼠灌胃CMTD(100 mg·kg^-1·d^-1),对照组和单纯照射组给予生理盐水。照射后第7天检测小鼠体重、脏器指数、脾脏T淋巴细胞亚群、B淋巴细胞亚群、NK细胞亚群变化以及脾脏组织病理学改变。结果分割照射对小鼠体重影响不大,但可诱发远端效应,使脾脏脏器指数降低为(0.369±0.011),与对照组的(0.396±0.022)比较,差异有统计学意义(t=2.978,P<0.05);改变脾脏病理结构,脾脏CD3+、CD4+、CD8+、CD3+CD4+、CD3+CD8+淋巴细胞比例显著降低(t=5.754、3.570、4.442、5.281、4.570,P<0.05)。而照射给药组小鼠体重恢复明显,脾脏组织损伤缓解,脾脏淋巴细胞亚群比例恢复,CD3+、CD3+CD4+、CD3+CD8+淋巴细胞显著升高(t=3.523、2.706、2.520,P<0.05),但仍低于正常水平。结论CMTD可有效改善X射线分割照射对小鼠脾脏的损伤,提高照后小鼠的免疫功能,可作为潜在的抗辐射治疗药物。     

The effects of low and normal dose ice slurry ingestion on endurance capacity and intestinal epithelial injury in the heat

ObjectivesCompare the effects of ice slurry ingestion at low and normal doses on endurance capacity and exertional heat stress-induced gastrointestinal perturbations.DesignRandomised, cross-over design.MethodsTwelve physically active males completed four treadmill running trials, ingesting ice slurry (ICE) or ambient drink (AMB) at 2 g·kg⁻¹ (Normal; N) or 1 g·kg⁻¹ (Low; L) doses every 15-min during exercise and 8 g·kg⁻¹ (N) or 4 g·kg⁻¹ (L) pre- and post-exercise. Pre-, during and post-exercise serum intestinal fatty-acid binding protein ([I-FABP]) and lipopolysaccharide ([LPS]) concentrations were determined.ResultsPre-exercise gastrointestinal temperature (T_gi) was lower in L + ICE than L + AMB (p < 0.05), N + ICE than N + AMB (p < 0.001) and N + ICE than L + ICE (p < 0.001). Higher rate of T_gi rise (p < 0.05) and lower estimated sweat rate (p < 0.001) were observed in N + ICE than N + AMB. Rate of T_gi rise was similar at low dose (p = 0.113) despite a lower estimated sweat rate in L + ICE than L + AMB (p < 0.01). Time-to-exhaustion was longer in L + ICE than L + AMB (p < 0.05), but similar between N + ICE and N + AMB (p = 0.142) and L + ICE and N + ICE (p = 0.766). [I-FABP] and [LPS] were similar (p > 0.05).ConclusionsL + ICE elicited a lower heat dissipation compensatory effect with similar endurance capacity as N + ICE. Ice slurry conferred no protection against exertional heat stress-induced gastrointestinal perturbations.     

褪黑素对照射后小鼠血小板造血的保护作用

目的探讨褪黑素(melatonin,Mel)对照射后小鼠血小板和巨核细胞造血功能的影响。方法18只雌性BALB/c小白鼠随机分为3组正常组(N组),对照组(C组)和Mel组(M组),每组6只。其中N组不接受照射和药物注射,C组和M组小鼠予4Gy的60Coγ射线全身照射,照射后M组每天腹腔注射Mel10mg.kg-1.d-1,连续注射21d,C组注射生理盐水。于照射前及照射后的第7、14和21天采尾血,观察白细胞和血小板计数变化,在第21天采血后取骨髓行巨核细胞集落形成单位(CFU-MK)和骨髓基质细胞集落形成单位(CFU-F)培养。另外观察正常小鼠体外骨髓CFU-MK在不同浓度的Mel(0～500nmol/L)作用下的生长情况。结果M组血小板计数回升明显高于C组(P<0.05),M组的CFU-MK和CFU-F集落生长明显优于C组(P<0.001)。体外小鼠骨髓CFU-MK的生长对Mel有浓度依赖性,Mel浓度为200nmol/L时,CFU-MK集落数目最多,且集落大小和MK成熟度较对照均有明显提高。结论Mel对照射后小鼠骨髓的血小板造血功能有保护作用,Mel可促进骨髓基质细胞和MK增殖分化,从而提升外周血血小板数量。     

不同寄主上的桑寄生药材毒性的比较研究

目的： 比较研究不同寄主来源的桑寄生（Taxillus sutchuenensis）药材的毒性。方法： 对6种不同寄主上的桑寄生药材进行急性毒性实验,测定半数致死量（LD₅₀）或最大耐受量（MTD）。并根据寄主来源不同,将98只昆明种小鼠随机分为对照组、沙梨组、李树组、白杨组、柞木组、夹竹桃组和漆树组,除对照组,其余各组小鼠每日ig 7.5 g·kg^-1水提物1次,共4周。测定血清中天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）及肌酐（Cr）、尿素氮（BUN）含量,并观察肝、肾组织病理改变。结果： 夹竹桃上的桑寄生、漆树上的桑寄生毒性明显,LD₅₀及95%可信限分别为109.276 （96.837~122.645） g·kg^-1和77.286（66.891~89.296）g·kg^-1;其余4种寄主上的桑寄生药材未出现死亡。与对照组比较,夹竹桃上的桑寄生能引起Cr指标的升高,并对小鼠肾组织影响较明显;而其他各寄主上的桑寄生组肝、肾功能检测指标差异不明显,对小鼠肝、肾组织损伤也较轻。结论： 寄主为夹竹桃、漆树有毒木类的桑寄生药材有明显的毒性。     

Radiosensitization of Chinese Hamster Cells by Oxygen and Misonidazole at Low X-ray Doses

Summary

The radiosensitization of Chinese hamster V79 cells in vitro by air and misonidazole at low X-ray doses (0·2–6·0 Gy) had been studied. These survival data, together with high-dose data, were fitted to the linear quadratic model ln S = ?(αD + βD²), deriving estimates of α and β by six different methods to illustrate the influence of the statistical treatment on the values so derived. This in vitro study clearly demonstrated that the survival parameters α and β are dependent to some degree on the method of analysis of the raw survival data; however, their ratios, the values of oxygen enhancement ratios (OERs) and radiosensitizer enhancement ratios (SERs) derived from the different methods, are similar. All methods of analysis give reduced OERs at low radiation doses for combined low- and high-dose X-ray data. However, the OERs are still appreciably high, ranging from 2·45 to 2·50 for an oxic dose of 2 Gy. All methods of analysis gave reduced SERs at low doses for combined low and high X-ray dose data for hypoxic cells irradiated in 1 mmol dm^?3 misonidazole. At survival levels corresponding to doses of 2 Gy in the presence of 1 mmol dm^?3 misonidazole and SERs ranged from 1·2 to 1·5.     

Mitochondrial DNA deletions in tissues of mice after ionizing radiation exposure

Purpose: The objective of the study was to estimate the presence of large mtDNA deletions in brain and spleen tissues of mice four months after exposure to 2 and 5?Gy.

Materials and methods: The male BALB/c mice underwent X-ray total-body acute radiation. Four months after irradiation, the mice were decapitated, and the samples of spleen and brain tissues were examined. A long-distance PCR was used to detect mtDNA deletions and their levels in samples of brain and spleen tissues.

Results: Four months after irradiation the levels of mtDNA deletions in the brain and spleen tissues were higher in animals exposed to 5?Gy than in animals at an irradiation dose of 2?Gy and in control mice. The levels of deletions in the mice brain tissues were higher 4 months than 1 month after X-ray exposure to both doses (2 and 5?Gy). In spleen tissues, a higher level of deletions was observed only at an irradiation dose of 5?Gy.

Conclusions: Our data have shown that ionizing radiation induces an increase of mtDNA copies with deletions in tissues of mice four months after the post-irradiation period. The level of deletions depends on the animal age, type of tissue, irradiation dose and length of the post-irradiation period.     

Additivity of Type O and Type N Damage in Diploid Yeast

Summary

Idiopathic pneumonitis is a major cause of morbidity and mortality in patients with leukaemia undergoing total body irradiation (TBI) and bone marrow transplantation (BMT). The effect of variation in dose rate of TBI on the development of lethal and sublethal lung damage has been investigated in mice by measuring changes in carbon monoxide uptake. CBA mice were irradiated using a ⁶⁰Co source at 0·02, 0·05, 0·1, 0·2, 0·5 and 1·0 Gy min^?1 to a total dose of 15·5 Gy. A log–linear relationship between the severity of impairment of carbon monoxide uptake (V_CO) and dose rate was found. Ventilatory requirement (ventilation rate/V_CO) was raised 20 to 40 weeks after TBI at dose rates above 0·1 Gy min^?1. Time of onset and extent of elevation of ventilatory requirement were also dose-rate dependent. The implications of these findings for clinical practice are discussed.     

Lung Tumour Induction in Mice after X-rays and Neutrons

Summary

Dose–response curves were determined for pulmonary adenomas and adenocarcinomas in mice after single acute doses of 200 kVp X-rays and cyclotron neutrons (E¯ = 7·5 MeV). A serial-killing experiment established that the radiation induction of chromosome aberrations. The validity of the concept of PLD neous cancers. The dose versus incidence (I) of tumours in male and female mice for X-ray doses between 0·25 and 7·5 Gy is ‘bell-shaped’ and best fitted with a purely quadratic induction and exponential inactivation terms, i.e. I = A + BD²e^?αD. In contrast, the tumour dose–response after 0·1–4·0 Gy of neutrons is best fitted by I = A + BD e^?αD and is steeply linear ≤ 1 Gy, peaks between 1 and 3 Gy and sharply declines at 4·0 Gy. The data for the female mice ≤ 1 Gy neutrons are best fitted to the square root of the dose.

A major objective of the experiments was to derive neutron RBE values. Because of the differences between the X-ray (quadratic) and neutron (linear) curves, the RBE_n will vary inversely with decreasing X-ray dose. The RBE values at 1 Gy of X-rays derived from the B coefficients in the above equations are 7·4 ± 3·2 (male and female); 8·6 ± 3·6 (female) and 4·7 ± 1·8 (male). These are high values and imply even higher values at the doses of interest to radiation protection. If, however, one restricts the analysis to the initial, induction side of the response (≤ 1 Gy neutrons, ≤ 3 Gy X-rays) then good linear fits are obtainable for both radiations and indicate neutron RBE values of 7·4 ± 2·3 for female mice and 4·5 ± 1·8 for males, and these are independent of dose level.     

Effects of Radiation and Other Influences on Chemical Lymphomagenesis

Summary

Methylnitrosourea (MNU) or butylnitrosourea (BNU) was used to induce T cell lymphomas (thymomas) in BDF₁ mice. In addition to the chemical, X-rays in various dose schedules were applied. An effect of the irradiation (shortening of the latency period) was seen with 12 × 0·25 Gy in protocols with a prolonged median induction time in the controls as a result of a dose reduction of the chemical (median induction time 27–36 weeks instead of 16–18 weeks under ‘optimal’ conditions using 50 mg kg^?1 of MNU). Preirradiation 2–5 weeks before 40 mg kg^?1 of MNU resulted in enhanced leukaemogenesis. Also, mice with regenerating lympho-haemopoiesis after lethal irradiation and bone marrow transplantation were more sensitive to the effect of both chemicals than were the controls. Treatment with anti-thy 1·2 and with corynebacterium parvum during the latency period had no influence.