APCmin/+小鼠缺失维生素D受体对肠道肿瘤生长的影响

目的 探讨维生素D受体(VDR)失活对APCmin/+小鼠肠道肿瘤生长的影响及机制.方法 通过构建APCmin/+VDR-/-小鼠模型(n=8),与APCmin/+小鼠比较(n=8),4月龄时观察肠道肿瘤大小及数目情况,肿瘤作HE染色以判断病理类型,免疫组化检测肿瘤相关基因BCL-2、vimentin-1、Stat-1和MSH-2蛋白的表达.结果 4月龄时2组鼠比较,APCmin/+VDR-/-小鼠>3 mm肿瘤明显增多(P<0.01).HE染色显示肠道肿瘤为管状腺瘤.APCmin/+肿瘤的Stat-1表达较强,而MSH-2和vi-mentin-1表达在APCmin/+VDR-/-肿瘤中均更强.结论 维生素D受体缺失促使APCmin/+小鼠肠道肿瘤的发展.     

维生素D受体在肠道肿瘤生长中与β-catenin通路之间的关系

目的探讨维生素D受体（VDR）对肠道肿瘤生长的影响以及与β-catenin信号通路之间的关系。方法体外培养的人类结肠癌SW480细胞株经维生素D处理4h,免疫沉淀法检测VDR和t3-catenin蛋白的交互作用,24h后用Westernblot检测细胞E．cadherin蛋白的表达。体内实验比较APCmin／＋VDR-／-与APCmin／＋小鼠,免疫组化法检测两型小鼠肠道肿瘤VDR、β-catenin和Brdu蛋白的表达,Westernblot检测肿瘤和肿瘤旁组织β-catenin蛋白的表达。结果维生素D处理SW480细胞后,VDR和β-catenin蛋白相互结合,随后E-cadherin蛋白表达增高（对照组灰度值145．57±4．21,实验组109．35±3．56,t=32．63,P〈0．05）。缺失VDR的APCmin／＋VDR-／-小鼠肠道肿瘤中β-catenin蛋白表达免疫组化（灰度值140．51±2．57）及Westemblot（灰度值166．47±2．36）检测均高于APCmin／＋肿瘤（分别为145．41±3．62、182．35±3．24,t=2．65,4．36,P〈0．05）。结论维生素D抑制肠道肿瘤增殖的作用可能通过VDR影响β-catenin信号通路来完成。     

抑癌候选基因NDRG2在膀胱肿瘤中的表达研究

目的 探讨N-myc下游调节基因(NDRG2)在膀胱正常组织和膀胱肿瘤组织中的表达情况,以及NDRG2的表达与膀胱肿瘤病理分级和临床分期的关系.方法 应用免疫组化SP法检测52例膀胱癌、10例膀胱乳头状肿瘤及10例膀胱正常组织石蜡标本中NDRG2表达情况,并进行相关临床病理分析.结果 NDRG2在正常膀胱组织阳性表达率为80.0％ (8/10),在膀胱肿瘤组织中阳性表达率为40.3％ (25/62),两者比较差异有统计学意义(x2=3.98,P＜0.05);NDRG2的阳性表达与膀胱肿瘤病理分级呈负相关(r=-0.288,P＜0.05),与C-myc表达呈负相关(r=-0.436,P＜0.01),与p53表达呈正相关(r=0.717,P＜0.01).结论 NDRG2基因在膀胱肿瘤组织中的表达水平随恶性程度的增高而降低,提示该基因可能对膀胱肿瘤病理分级和临床分期有一定的指导意义.     

哮喘大鼠肺组织Ca^2＋/CaN-NFATc活性及其与TH1/TH2失衡的关系

目的 探究哮喘大鼠肺组织Ca^2＋/CON-NFATc的活性及其与TH1/TH2失衡的关系.方法 24只Wistar大鼠随机分为哮喘组和对照组,12只/组.用鸡卵白蛋白（OVA）溶液致敏和激发复制大鼠哮喘模型.Maclab系统记录分析大鼠肺功能;HE染色观察气道炎症并测量气道管壁厚度;检测肺组织钙含量、CaN活性、去磷酸化NFATc蛋白的表达及IL-4、IL-2的含量.结果 与对照组相比,哮喘组大鼠支气管管壁厚度明显增加（t=-7.99,P〈0.01）;气道阻力和呼吸频率增加（t=2.59,P〈0.05;t=7.94,P〈0.01）,每分通气量减少（t=6.87,P〈0.01）;与对照组相比,哮喘组大鼠肺组织中IL-4含量和IL-4/IL-2比值增高（t=-8.69,11.40,P〈0.01）,而IL-2含量降低（t=8.29,P〈0.01）;与对照组相比,哮喘组大鼠肺组织中CaN活性和去磷酸化NFATc蛋白的相对表达量均增加（t=-2.91,-22.45,P〈0.01）,而肺组织钙含量降低（t=4.75,P〈0.01）;肺组织中CaN活性与去磷酸化NFATc蛋白的相对表达量呈正相关（r=0.39,P〈0.05）;去磷酸化NFATc蛋白的相对表达量与IL-4/IL-2比值呈正相关（r=0.83,P〈0.01）;而肺组织中IL-4/.IL-2比值与大鼠支气管管壁厚度成正相关（r=0.84,P〈0.01）.结论 哮喘大鼠肺组织中CaN-NFATc的活性增加,其活性的增加可促进IL-4/IL-2比值增加,推测CaN-NFATc信号通路可能参与了哮喘大鼠肺组织TH1/TH2失衡的形成.     

哮喘小鼠肺内HMGB1及TLR2的表达及1,25-(OH)_2D_3的干预作用

目的观察高迁移率族蛋白B1(HMGB1)及Toll样受体2(TLR2)在哮喘小鼠肺内的表达,及1,25-二羟基维生素D3(1,25-(OH)_2D_3)对二者表达的影响。方法将30只BALB/c小鼠随机分为3组:对照组、哮喘组和干预组,应用HE染色方法观察各组小鼠肺组织形态学改变,并测定相同级别支气管气道壁厚度,免疫组化法观察HMGB1、TLR2的表达,RT-PCR方法测定各组小鼠肺内HMGB1mRNA及TLR2mRNA的表达。结果哮喘组小鼠肺内HMGB1及TLR2的表达均高于对照组,干预组二者的表达明显低于哮喘组,差异均有统计学意义(P0.05);哮喘组气道壁厚度高于对照组及干预组,差异有统计学意义(P0.05)。结论 HMGB1和TLR2参与了哮喘的发病过程;1,25-(OH)_2D_3能抑制HMGB1及TLR2在哮喘小鼠肺内的表达,且在具有抑制哮喘小鼠气道重塑的作用。     

APP/PS1双转基因小鼠的认知功能、炎症与肠道菌群特征分析

目的 探究阿尔茨海默症动物模型APP/PS1双转基因小鼠的认知功能、炎症及肠道菌群特征。方法 15只3月龄WT雄性小鼠为对照组,15只3月龄APP/PS1双转基因小鼠为模型组,饲养6个月后进行水迷宫实验,观察潜伏期。实验结束后采集小鼠血清、海马组织和粪便,测定小鼠血清细胞因子、海马Aβ蛋白沉积和细胞因子表达情况以及肠道菌群多样性和群落结构。结果 APP/PS1组小鼠海马中有明显的Aβ蛋白沉积、水迷宫潜伏期显著增加(t=-2.16;t=-3.20,P<0.05)。WT组小鼠血清LPS水平显著高于APP/PS1组(t=2.97,P<0.01),IL-1β水平显著低于APP/PS1组(t=-3.69,P<0.01)。APP/PS1组小鼠海马组织中BDNF mRNA表达水平显著高于WT组(Z=-2.79,P<0.01)。APP/PS1双转基因小鼠的肠道菌群Alpha多样性显著低于WT组(t=3.01,P<0.05),Beta多样性分析表明两组群落结构具有显著差异(R=0.45,P<0.05);APP/PS1组的疣微菌门和阿克曼氏菌属的相对丰度显著低于WT组(Z=2.61,P<0.05)。结论 APP/PS1组出现明显的认知功能下降、炎症反应以及肠道菌群结构的异常改变。肠道菌群可能是防治阿尔茨海默症的新靶点,值得进一步研究。     

高脂饮食对载脂蛋白E缺乏鼠维生素D受体表达及一氧化氮合酶活性影响研究

目的了解高脂饮食对载脂蛋白（apoE）缺乏鼠（apoE^-/-）维生素D受体（VDR）表达及内皮型一氧化氮合酶（eNOS）活性影响,探讨VDR在动脉粥样硬化（AS）形成的意义及可能机制。方法apoE^-／-小鼠与作为对照的C57BLP6J小鼠分别按数字表法分为正常食物组与高脂食物组,采用竞争蛋白结合放射免疫法检测小鼠血25-（OH）D水平,采用免疫荧光化学法及RT-PCR法检测小鼠主动脉VDR表达,应用硝酸还原酶法检测小鼠血一氧化氮（NO）含量和eNOS酶活力。结果高脂饮食进一步加重apoE-/-小鼠As病变、降低血25-（OH）D水平[血25-（OH）D：正常饲料C57BLP6J小鼠、高脂饲料C57BLP6J小鼠、正常饲料apoE。一小鼠、高脂饲料apoE-/-小鼠分别为[（26．44±1．28）ng／mL、（22．68±2．07）ng／mL、（1-7.46±4.2．22）ng／mL、（15．88±0．97）ng／mL,P〈0．01]。高脂饮食进一步上调apoE-/-小鼠主动脉VDR蛋白与mRNA表达水平[VDR蛋白分别为0．244±0．088、0．346±0．132、0．547±0．128、0．768±0．162,VDtlmRNA分另U为、0．228±O．08．3、0．375±0．103、0．451±0．117、0．597±0．131,P均〈0．01]。高脂饮食致apoE一小鼠血NO水平、eNOS酶活力明显增高[NO：（39．74±4．81）μmol／L、（48．1±5．24）ixmol／L、（67．34±6．14）tzmol／L、（86．74±8．05）txmol／L;eNOS：（8．6-t-O．77）u／L、（12．28±1．42）U／L、（15．96-t-O．92）U／L、（18．68±1．15）U／L,P均〈0．01]。血25-（OH）D水平与血浆中NO含量、eNOS酶活力及VDR表达呈负相关（P〈0．01）。结论apoE-/-小鼠血25-（OH）D水平降低,VDR表达量明显上调,血NO含量、eNOS酶活力增高,高脂饮食可进一步降低血25-（OH）13、NO水平,上调主动脉VDR表达,增加eNOS酶活力。高脂饮食、维生素D、apoE相互作用,影响As病变可能与NO、eNOS有关。     

妊娠期母体使用抗生素和益生菌对后代小鼠肠道发育和肠道菌群的影响

目的 探究妊娠晚期使用头孢曲松和两歧双歧杆菌TMC3115对断乳期小鼠肠道上皮组织发育及肠道菌群构建的影响。方法 24只妊娠10～13 d BALB/C小鼠随机分为对照组、头孢曲松组和TMC3115组(n=8)。妊娠期小鼠分别每日用生理盐水、头孢曲松(30 mg/d)、TMC31115菌悬液（含菌量为109 CFU/d）灌胃至分娩，新生小鼠由母鼠母乳喂养至断乳期（PND21）。采用HE染色观察小鼠结肠绒毛和隐窝深度；RT-PCR法检测各组小鼠肠道上皮组织发育相关蛋白(Ki67、Muc2)和紧密连接蛋白（ZO-1、Claudin-1、Claudin-2、Occludin）表达;二代测序法分析小鼠肠道菌群组成。结果 和对照组和头孢曲松组相比，TMC3115组小鼠的结肠隐窝深度、KI67 mRNA表达量显著(P<0.05)升高。TMC3115组小鼠紧密连接蛋白Occludin mRNA表达量也显著高于对照组(P<0.05)。对照组和TMC3115组肠道菌群中厚壁菌门相对丰度，头孢曲松组拟杆菌门相对丰度最高。和头孢曲松组相比，TMC3115组厚壁菌门和乳杆菌属相对丰度显著升高(P&...     

北京地区0～6月龄母乳喂养儿维生素D营养状况及相关骨代谢指标评估

目的 研究北京地区0~6月龄母乳喂养儿的维生素D水平变化及与相关指标BAP、PTH的关系,为今后的婴儿保健工作提供数据支持。方法 选取健康新生儿,生后予规律补充维生素D400 IU/d至6月龄,在0、4、6月龄分别取静脉血检测维生素D及BAP、PTH的水平,评估北京地区母乳喂养儿维生素D的现状及各指标之间的关系。结果 0月龄组婴儿维生素D正常与良好的人数仅占28.8%, 经过规律补充维生素D,4月龄组此比值为82.8%,6月龄组为83%。0月龄组25-(OH)D₃水平与4月龄组呈显著正相关关系(r=0.481,P＜0.01),4月龄组BAP及PTH均与血25-(OH)D₃水平呈负相关关系(r=-0.485和-0.216,P＜0.05)。结论 北京地区新生儿血维生素D水平较低,经过规律补充维生素D大部分婴儿可达正常水平,婴儿出生时25-(OH)D₃储备可能对婴儿早期25-(OH)D₃水平产生一定的影响。     

STAT-3及其相关因子在新生鼠巨细胞病毒感染中的表达及意义

目的:探讨信号转导和转录激活子3(STAT-3)及其相关转录因子在新生鼠巨细胞病毒(MCMV)感染中的表达变化及其意义.方法:48只新生BALB/c小鼠按窝随机分为病毒组(n=24)和对照组(n=24).两组动物均设3天、7天、14天3个时间点亚组,各亚组平均8只小鼠.病毒组于仔鼠出生3天时腹腔接种致半数细胞感染量为104.31 μ/0.1 ml的MCMV病毒悬液20μl,建立MCMV播散性感染模型;对照组腹腔注射等量的无菌生理盐水.各组于规定时间点处死仔鼠,HE染色观察仔鼠肝、脾、肺组织病理改变;半定量RT-PCR法检测脾脏STAT-3mRNA、孤独核受体(RORγt) mRNA及白介素-17 (IL-17) mRNA的表达.结果:①病毒组小鼠肝、脾、肺组织MCMV-DNA PCR检测出现阳性条带,HE染色出现相应病理改变.②病毒组小鼠脾组织STAT-3mRNA、RORγtmRNA及IL-17 mRNA的表达水平在感染后7天、14天明显高于对照组(P＜0.01).结论:STAT-3及其相关因子的高表达可能促进巨细胞病毒在体内的复制,为巨细胞病毒感染的发病机制之一.     

mB7-1-GPI融合蛋白锚定Lewis细胞疫苗的制备及抗肿瘤作用

下载PDF阅读器目的 将mB7-1-GPI融合蛋白锚定于小鼠肺癌细胞株（Lewis）膜上,制备肿瘤细胞疫苗,研究该瘤苗的抗肿瘤作用.方法 将mB7-1-GPI融合蛋白锚定于小鼠肺癌细胞（Lewis）膜上,制备肿瘤细胞疫苗.采用流式细胞术检测该蛋白的细胞膜锚定作用.建立C57BL小鼠的肺癌模型,观察用mB7-1-GPI融合蛋白制备的肿瘤疫苗对荷瘤小鼠的免疫治疗作用.结果 mB7-1-GPI与Lewis瘤细胞共同孵育4 h后4℃放置0、4 h和8 h,样本的荧光强度分别为11.2、10.6和9.8,阳性细胞数百分率分别为95.8%、93.6%、91.1%.脾细胞＋Lewis组IL-2和IFN-γ分泌量分别为（25.9±1.4）pg/ml、（56.0±3.5）pg/ml,脾细胞＋Lewis/mB7-1-GPI组IL-2和IFN-γ分泌量分别为（871. 3±10.4）pg/ml和（1329.0±11.9）pg/ml,25 d时,Lewis/mB7-1-GPI瘤苗组小鼠的肿瘤直径（1.4±0.21）cm较Lewis瘤苗治疗组小（2.5±0.27）cm,差异有统计学意义（P＜0.05）.Lewis/mB7-1-GPI瘤苗组小鼠寿命为（75.2±2.0）d,与Lewis瘤苗组（40.2±1.3）d相比,生存期延长,差异有统计学意义（P＜0.05）.结论 mB7-1-GPI融合蛋白制备的肿瘤疫苗具有较强的抗肿瘤作用,有可能作为一种有效的新型疫苗用于肿瘤的治疗和预防.     

Inhibitory effects of calcium against intestinal cancer in human colon cancer cells and ApcMin/+ mice

The aim of the study was to investigate the inhibitory effects of calcium against intestinal cancer in vitro and in vivo. We first investigated the effects of calcium treatment in HCT116 and HT29 human colon cancer cells. At the concentration range of 0.8-2.4 mM, calcium significantly inhibited cell growth (by 9-29%), attachment (by 12-26%), invasion (by 15-31%), and migration (by 19-61%). An immunofluorescence microscope analysis showed that the treatment with calcium (1.6 mM) for 24 h increased plasma membrane β-catenin but decreased nuclear β-catenin levels in HT29 cells. We then investigated the effect of dietary calcium on intestinal tumorigenesis in Apc^Min/+ mice. Mice received dietary treatment starting at 6 weeks of age for the consecutive 8 weeks. The basal control diet contained high-fat (20% mixed lipids by weight) and low-calcium (1.4 mg/g diet) to mimic the average Western diet, while the treatment diet contained an enriched level of calcium (5.2 mg calcium/g diet). The dietary calcium treatment decreased the total number of small intestinal tumors (by 31.4%; P < 0.05). The largest decrease was in tumors which were ≥ 2 mm in diameter, showing a 75.6% inhibition in the small intestinal tumor multiplicity (P < 0.001). Immunohistochemical analysis showed significantly reduced nuclear staining of β-catenin (expressed as nuclear positivity), but increased plasma membrane staining of β-catenin, in the adenomas from the calcium-treated groups in comparison to those from the control group (P < 0.001). These results demonstrate intestinal cancer inhibitory effects of calcium both in human colon cancer cells and Apc^Min/+ mice. The decreased β-catenin nuclear localization caused by the calcium treatment may contribute to the inhibitory action.     

Vitamin D deficiency enhances the growth of MC-26 colon cancer xenografts in Balb/c mice

Vitamin D deficiency has been associated with increased risk of colon cancer in epidemiologic and prospective clinical studies. In vitro and in vivo studies demonstrated that 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and its analogs inhibit colon cancer cell proliferation. Few studies have evaluated the effect of vitamin D deficiency on the development and growth of colon cancer. To assess the antiproliferative effects of 25-hydroxyvitamin D [25(OH)D] and 1,25(OH)2D3 in vitro, we cultured MC-26 (a colon cancer cell line) in the presence of 25(OH)D3 and 1,25(OH)2D3 and performed [3H]thymidine incorporation. The proliferation of MC-26 was significantly inhibited by both 25(OH)D3 and 1,25(OH)2D3. To determine the effect of vitamin D deficiency on colon cancer proliferation, Balb/c mice were rendered vitamin D deficient by feeding them a vitamin D-deficient diet for 3 mo. A group of vitamin D-sufficient mice was given the same diet with supplemental vitamin D. The mice were injected with MC-26 colon cancer cells and the tumors were measured daily for 20 d. Vitamin D-sufficient mice had 40% smaller tumors than vitamin D-deficient mice. The tumors were evaluated for mRNA expression of the vitamin D receptor (VDR) and 25-hydroxvitamin D-1alpha-hydroxylase (1alpha-OHase) by quantitative RT-PCR. The expression of the mRNA for the VDR and the 1alpha-OHase was 37- and 6-fold higher, respectively, in the vitamin D-sufficient mice compared with the vitamin D-deficient mice. We conclude that vitamin D deficiency enhances the growth of colon cancer in mice. The tumor expression of VDR and 1alpha-OHase indicates possible autocrine/paracrine cell growth regulation by vitamin D.     

High Dietary Niacin May Increase Prostaglandin Formation but Does Not Increase Tumor Formation in Apc Min/+ Mice

High doses of niacin (nicotinic acid) used to treat dyslipidemias cause flushing, due to high levels of prostaglandin D₂ (PGD₂). GPR109A, a G-protein coupled receptor, triggers the flushing in the skin. In addition to boosting PGD₂, niacin binding to GPR109A activates the entire prostanoid cascade. We found that GPR109A occurs throughout the gastrointestinal tract. Mice that alternated between a 1% niacin diet and a control diet had higher urinary prostaglandin E₂ (PGE₂) metabolite levels when on niacin (2.8-fold increase; 95% confidence interval, 1.8–3.9). PGE₂ promotes tumors in the intestines, whereas PGD₂ may have an opposite effect, on the basis of our report showing that transgenic hematopoietic prostaglandin D synthase suppresses intestinal adenomas in Apc ^Min/+ mice. To determine if either tumor growth or tumor suppression prevails, we fed Apc ^Min/+ mice a 1% niacin diet and assessed tumor development. A 1% niacin diet did not affect the number of tumors scored histologically in Apc ^Min/+ mice at 14 wk (33 mice on niacin, 33 controls). Although niacin stimulates production of various prostaglandins, our results support an interpretation that very high intakes of niacin are safe in relation to intestinal tumors in this model.     

Adiposity-Related Protection of Intestinal Tumorigenesis: Interaction With Dietary Calcium

Although high-calcium diets have been reported to reduce the risk of colorectal cancer, our preliminary data with the adenomatous polyposis coli (Apc) Min mutation (Min/+;Apc^Min/+) mouse shows a paradoxical increase in intestinal tumor loads (> 65%) with high calcium diets. Since we previously demonstrated that increasing dietary calcium reduces adiposity, and Apc^Min/+ mice on high calcium diets exhibited profound loss of adipose tissue, we hypothesized that loss of an adipose tissue-derived tumor suppressor factor(s) resulted in increased tumor susceptibility in animals on the high calcium diet. Accordingly, tumor prone Apc^Min/+ mice were crossed with obesity prone lethal yellow agouti (A ^y /a) mice to generate obese A^y/Apc^Min/+ mice. Low (0.2%), normal (0.5%), and high (1.2%) calcium diets were fed to both A^y/Apc ^Min/+ mice and Apc^Min/+ mice from 35–40 days until 90 days of age (n = 21/strain, n = 7/diet group). The high calcium diet reduced weight gain in both strains (P < 0.01) and reduced fat pad mass by 46–57% in A ^y /Apc^Min/+(P < 0.004) and by 65–82% in Apc^Min/+(P < 0.03).Apc^Min/+ mice on the high calcium diet exhibited an increase in tumor number (76 vs. 29, P = 0.009), but this effect was not seen in the A^y/Apc^Min/+ mice.β-Catenin and cyclin D1 gene expression were significantly induced with high calcium diet in intestinal tumor tissue of Apc^Min/+ mice but not in A^y/Apc^Min/+ mice. We conclude that the differential effect of dietary calcium on intestinal tumorigenesis in lean vs. obese Apc^Min/+ may result from the loss of adipose-derived protective factor(s) due to the substantial loss of body fat in Apc^Min/+ mice fed a high calcium dairy diet, increasingβ-catenin and cyclin D1 in tumors.     

Vitamin D Receptor Protects against Radiation-Induced Intestinal Injury in Mice via Inhibition of Intestinal Crypt Stem/Progenitor Cell Apoptosis

It is urgent to seek new potential targets for the prevention or relief of gastrointestinal syndrome in clinical radiation therapy for cancers. Vitamin D, mediated through the vitamin D receptor (VDR), has been identified as a protective nutrient against ionizing radiation (IR)-induced damage. This study investigated whether VDR could inhibit IR-induced intestinal injury and explored underlying mechanism. We first found that vitamin D induced VDR expression and inhibited IR-induced DNA damage and apoptosis in vitro. VDR was highly expressed in intestinal crypts and was critical for crypt stem/progenitor cell proliferation under physiological conditions. Next, VDR-deficient mice exposed to IR significantly increased DNA damage and crypt stem/progenitor cell apoptosis, leading to impaired intestinal regeneration as well as shorter survival time. Furthermore, VDR deficiency activated the Pmaip1-mediated apoptotic pathway of intestinal crypt stem/progenitor cells in IR-treated mice, whereas inhibition of Pmaip1 expression by siRNA transfection protected against IR-induced cell apoptosis. Therefore, VDR protects against IR-induced intestinal injury through inhibition of crypt stem/progenitor cell apoptosis via the Pmaip1-mediated pathway. Our results reveal the importance of VDR level in clinical radiation therapy, and targeting VDR may be a useful strategy for treatment of gastrointestinal syndrome.     

Intestinal tumorigenesis in Min mice is enhanced by X-irradiation in an age-dependent manner

We examined the effect of X-irradiation on intestinal tumorigenesis in Min (multiple intestinal neoplasia) mice. Single whole-body irradiation was given to mice of various ages from newborn to young adults. On the C57BL/6J (B6) background, X-irradiation increased tumor multiplicity of the small intestine exposed at ages from 2-3 days to 24-25 days, with a peak of 2.7-fold increase at 10-12 days of age; exposure at later ages resulted in only a slight increase. X-irradiation also increased colonic tumors; however, the susceptible age period appeared earlier than that of the small intestine; the peak value of 4.6-fold increase was observed in the exposure at around 2-3 days of age. Irradiation at 24 days or later ages showed almost no effect on the colonic tumor induction. On the (B6 x MSM)F1 background, X-irradiation resulted in 2.7-fold increase in the small intestinal tumors, but no increase in the colonic tumors, and besides, the age dependency observed in the small intestinal tumors was much attenuated. Collectively, we conclude that tumorigenic efficacy of X-irradiation in Min mice was determined by the combination of the target organ, the age at exposure, and the genetic background.