膳食纤维与植酸对1,2-二甲肼诱导大鼠结直肠癌发生的作用

目的:考察膳食纤维与植酸对动物模型结直肠癌发生的作用。方法:用86只4w龄雄性Wistar大鼠,按体重随机分为纤维素组、果胶组、植酸组、纤维素+植酸组、果胶+植酸组和对照组六组,用1,2-二甲肼(DMH)皮下注射诱发结直肠癌,观察大鼠结直结直肠肿瘤的发生率、肿瘤的数量及体积;测定大鼠结肠粘膜细胞的增殖活性。结果:各组大鼠结直肠肿瘤的发生率与对照组相比无显著性差异,但植酸组平均每只鼠的肿瘤个数和肿瘤体积显著低于对照组;果胶组、果胶+植酸组平均每只鼠的肿瘤个数显著高于对照组。植酸组大鼠结直肠粘膜细胞的增殖活性比对照组显著降低。果胶组大鼠结直肠粘膜细胞的增殖活性比对照组显著升高。结论:膳食中添加果胶能增加诱癌大鼠患结直肠肿瘤的危险,而饮水中添加2%的植酸可降低诱癌大鼠患结直肠肿瘤的危险。     

肌醇六磷酸对诱癌大鼠大肠组织抗氧化活性的影响

目的建立大鼠大肠癌动物模型,观察肌醇六磷酸(植酸)对诱癌大鼠大肠组织抗氧化活性的影响。方法30只4周龄雄性Wistar大鼠按体重随机分为植酸组和对照组,每组15只。植酸组饮水添加2%植酸钠,对照组自由饮水。2组大鼠均给予皮下注射1,2-二甲肼(DMH),观察肿瘤发生率、肿瘤的数量及体积;测定大肠组织的超氧化物岐化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性和丙二醛(MDA)含量。结果植酸组大肠癌发生率与对照组相比差异无显著性,植酸组平均每只鼠的肿瘤个数、肿瘤体积均显著低于对照组(P<0.01,P<0.05);植酸组大鼠大肠组织的SOD、GSH-Px活性比对照组显著升高(P<0.01),MDA含量显著降低(P<0.01)。结论植酸可降低诱癌大鼠大肠肿瘤发生的危险,可能通过其抗氧化作用发挥抗肿瘤作用。     

中药方剂对结直肠癌化疗患者免疫功能和骨髓抑制的影响

目的探讨中药升血方剂对结直肠癌化疗患者免疫功能和骨髓抑制的影响。方法选取2017年1月至12月本院收治的结直肠癌患者80例,随机分为观察组和对照组,每组40例。两组患者均采取XELOX方案化疗,观察组在此基础上加用中药升血方剂,均连续治疗6 w。评估两组临床疗效,比较患者免疫功能相关指标、骨髓抑制程度及生活质量。结果观察组治疗有效率为25.00%,明显高于对照组的15.00%,差异有统计学意义(P<0.05);观察组治疗稳定率为67.50%,明显高于对照组的40.00%,差异有统计学意义(P<0.05)。治疗6 w后,观察组CD+4、CD+4/CD+8及NK细胞活性明显高于治疗前且优于同期对照组,差异均有统计学意义(均P<0.05)。治疗6 w后,观察组患者骨髓抑制率明显低于对照组,差异有统计学意义(P<0.01)。治疗6 w后观察组患者生活质量评分明显高于治疗前和同期对照组,差异均有统计学意义(均P<0.05)。结论升血方剂可有效提升结直肠癌化疗患者的免疫功能,减轻骨髓抑制并提高生活质量。     

二甲双胍对糖尿病合并结直肠癌术后患者生存期的影响

目的探讨二甲双胍对糖尿病合并结直肠癌患者肿瘤切除术后生存期的影响。方法回顾性观察了于1988年1月~2012年12月在海军总医院治疗的糖尿病同时合并原发性结直肠癌患者140例,其中男性84例,女性56例,平均年龄(62.51±13.22)岁,采集患者年龄、性别、结直肠癌分期和术前测定的血色素、血糖、胆固醇、三酰甘油,并统计非酒精性脂肪肝、体质量指数和应用降糖药物的情况,依据其应用二甲双胍与否而分为二甲双胍组和对照组。结果 II期结直肠癌生存10年以上人数二甲双胍组(39.02%)和对照组(15.38%)的比较,差异具有统计学意义(P0.05),生存期二甲双胍组[(10.37±4.34)年]和对照组[(8.46±4.06)年]的比较,差异具有统计学意义(P0.05);III期结直肠癌生存5年以下人数二甲双胍组(39.29%)和对照组(71.88%)的比较,差异具有统计学意义(P0.05),生存5~10年人数二甲双胍组(39.29%)和对照组(15.63%)比较,差异具有统计学意义(P0.05),二甲双胍组[(7.24±5.90)年]生存期与对照组[(5.37±4.35)年]比较,差异无统计学意义(P0.05),二甲双胍组体质量指数(body mass index,BMI)偏低(P0.01)。通过多因素Logistic回归分析发现年龄(P0.05,OR=3.046)、肿瘤分期(P0.01,OR=0.232)和应用二甲双胍(P0.01,OR=3.297)是生存时间的相关因子。结论糖尿病合并结直肠癌患者肿瘤切除术后口服二甲双胍可以改善患者的生存期。     

抗性淀粉对氧化偶氮甲烷诱导的大鼠结(直)肠癌前病变预防作用研究

目的研究抗性淀粉(resistant starch,RS)对大鼠结(直)肠癌前病变的预防作用。方法将50只雄性Wistar大鼠随机分为阴性对照、阳性对照组及RS低、中、高剂量组。阳性对照组大鼠从实验第2w开始腹腔注射氧化偶氮甲烷(azoxymethane,AOM),1/w,连续2w。阴性对照组注射生理盐水。各剂量组用致癌剂处理与阳性对照组,并分别自由摄食含7.6%、15.2%及22.8%RS的饲料。对照组大鼠摄食普通饲料。于首次注射AOM后13w断头处死各组所有动物,观察并计数结肠变性隐窝病灶(aberrant crypt foci,ACF)发生情况。并取大肠组织标本,包埋后做石蜡切片,用SABC免疫组化法测量生物标记物增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)标记指数(PCNA-LI)、核仁组成区嗜银蛋白(argyrophilic nucleolar,organizer region protein,AgNORs)颗粒数目,以及Bcl-2蛋白(B-cell lymphomaleukemia-2,Bcl-2)、Bax蛋白(Bcl-2 associated X protein,Bcl-2)表达情况。结果与阳性对照组相比,各RS处理组ACF数目和AgNORs数目均显著降低(P<0.01),高剂量组增殖细胞核抗原标记指数(PCNA-LI)显著减少(P<0.05);此外,RS还抑制了Bcl-2蛋白的表达,诱导了Bax蛋白的表达。结论短期RS对AOM诱发的大鼠结(直)肠癌前病变具有预防作用,可使ACF和AgNQR3显著减少即其机制可能与抑制细胞增殖和诱导细胞凋亡有关。[营养学报,2013,35(2):158-161,166]     

麦草粉对单纯性肥胖大鼠胰岛素抵抗的影响

目的:探讨麦草粉对单纯性肥胖大鼠胰岛素抵抗及血糖的影响。方法:34只Wistar大鼠随机分成正常对照组、模型组和麦草粉组。模型组和麦草粉组以高脂饲料饲喂6w诱发大鼠肥胖模型,再灌胃给麦草粉4w,分批禁食20～24h,采尾血测定基础血糖,然后进行葡萄糖钳夹实验。结果:模型组基础血糖、胰岛素、TG、TCH、LDL和FFA明显高于对照组(P<0.05),麦草粉组与模型组比较,基础血糖、胰岛素、TG、TCH、LDL和FFA均呈非常显著降低(P<0.01),葡萄糖钳夹实验结果显示,麦草粉组葡萄糖输注速率(GIR)值非常显著高于模型组(P<0.01),增重率和脂肪垫比率显著低于模型组(P<0.05)。结论:麦草粉可降低单纯性肥胖大鼠的血糖,调节血脂,改善胰岛素抵抗,有一定的减肥作用。     

早期饲料构成对大鼠甲状腺素及肉碱棕榈酰转移酶-ⅠmRNA表达的影响

目的:研究早期饲料构成对高脂膳食大鼠体重、体脂含量、血糖、甲状腺素FT4及肝脏肉碱棕榈酰转移酶-Ⅰ(CPT-Ⅰ)mRNA水平的影响。方法:新生Wistar雄性大鼠24d断乳,按体重随机分为A、B、C、D四组,分别给予高碳水化合物构成的基础饲料、高蛋白质、高不饱和脂肪酸、与高饱和脂肪酸构成的饲料喂养3w后,基础饲料喂养2w。按体重将A组随机分为A1、A2两组。A1组喂饲基础饲料作为对照组,A2与B、C、D组给予高脂饲料喂养6w,结束实验;A2组为高碳水化合物对照组。每组32头大鼠,动态观察体重、体脂含量、血糖、甲状腺素(FT4)及肝脏CPT-ⅠmRNA水平。结果:实验末期,C组大鼠体重、体脂含量和血糖显著低于A2组(P<0.05)、甲状腺素FT4水平明显高于A2组(P<0.05);B组体重、体脂含量明显低于A2组(P<0.05),甲状腺素FT4水平明显高于A2组(P<0.05),但血糖水平高于A2组(P>0.05);D组大鼠体重明显低于A2组(P<0.05),血糖、体脂含量和甲状腺素FT4水平与A2无差异(P>0.05)。动态观察表明,实验中C组大鼠肝脏CPT-ⅠmRNA水平持续升高。结论:早期饲料构成可能通过影响甲状腺素水平、持续改变CPT-Ⅰ基因表达,影响高脂膳食大鼠的体重和体脂含量。     

中华麦饭石和有机锗（Ge—132）预报大鼠实验性大肠癌的研究

用二甲肼诱发Ｗｉｓｔａｒ大鼠大肠癌，同时分别服用１０％中华麦饭石浸泡液和有机锗（Ｇｅ－１３２）２７周。结果发现中华麦饭石组患癌率、每鼠平均癌灶数和平均癌灶体积无显著少于对照组和有机锗组（Ｐ〈０．０５）。有机锗组仅每鼠平均癌灶数和平均癌灶体积少于对照组（Ｐ〈０．０１），两组转移癌发生率均少于对照组（Ｐ〈０．０１），两组血清γ－干扰素滴度和脾细胞ＮＫ活性都高于对照组（Ｐ〈０．０５）。内镜检查显示两组结     

高脂饮食对大鼠胃促生长素表达的影响

目的研究高脂饮食对大鼠胃促生长素(ghrelin)表达的影响。方法雄性SD大鼠9只喂以基础饲料作为对照组(CF),27只喂以高脂饲料15w产生饮食诱导肥胖大鼠(DIO)14只和饮食诱导肥胖抵抗大鼠(DIO–R)7只,再将DIO大鼠随机分为两组,一组改用基础饲料(DIO–HF/LF),另一组继续用高脂饲料(DIO–HF)喂养至23w,对照组和DIO-R组饲料不变。分别于15w和23w末过夜禁食后,次晨采尾血或断头取血,检测空腹血糖和胰岛素含量,取胃底部组织用RT-PCR、免疫印迹方法检测ghrelin表达水平。结果DIO–HF/LF组体重显著低于DIO–HF组而高于CF组(P<0.05);DIO–R组与CF组体重无显著性差异。DIO–HF组胃ghrelin的表达低于DIO–HF/LF及CF组,与DIO–R组无显著性差异,DIO–HF/LF和CF组间无显著性差异。结论高脂饮食诱导的肥胖大鼠可通过降低胰岛素敏感性来减少ghrelin的表达。肥胖大鼠经过低脂干预后,可改善胰岛素敏感性从而增加胃内ghrelin的表达。高脂饮食诱导的肥胖抵抗大鼠胃内ghrelin表达低于对照组,故认为肥胖抵抗产生的原因之一是ghrelin的低表达限制了能量摄入。     

灵芝虫草菌丝体对大鼠NK细胞活性影响的流式细胞术研究

目的：研究灵芝与虫草菌丝体联合使用对SD大鼠NK细胞免疫调节的作用。方法：将灵芝虫草菌丝按0．75％和1．50％的比例掺入饲料中（分别相当于0．75g/kg、1．50g/kg BW剂量）给SD大鼠自由摄食，连续30d后取其外周血用流式细胞术检测NK细胞活性。结果：1．50g／kg BW剂量组大鼠外周血CD161a^-／CD25^＋和CD161a^＋／CD25^＋的表达明显高于对照组，差异比较有统计学意义（P〈0．05）。结论：灵芝虫草菌丝体有增强大鼠NK细胞活性的作用。     

T‐cell mitogenesis and natural killer cell activity in colonic tumor‐bearing and nontumor‐bearing rats fed diets high in lipid with and without cholesterol

It has been shown that rats fed diets high in lipid and cholesterol develop more 1,2‐dimethyl‐hydrazine (DMH)‐induced bowel tumors than those fed diets low in lipid or without cholesterol. To further explore the effects of these dietary regimens on immune function, rats were fed diets containing 20% safflower or coconut oil, with or without cholesterol (1 %) and cholic acid (0.3%), for 35 weeks during which time they were given DMH. Only rats bearing one or more colon tumors and that showed no evidence of weight loss were utilized. Two parameters of cell‐mediated immune function were assessed in tumor‐ and nontumor‐bearing control rats: a) response to the T‐cell mitogen, phytohemaglutinin (PHA), and b) natural killer cell activity (NKCA). Nearly total suppression of PHA response was observed in the polyunsaturated fat diet group compared with the saturated fat diet groups. Addition of cholesterol to either the polyunsaturated or saturated fat diets diminished PHA response and, to a lesser degree, of T‐lymphocytes from rats fed these diets. NKCA, however, was unaffected by either the quality of dietary fat or cholesterol. There were no detectable effects of DMH perse 15 weeks after the last injection (or in the presence or absence of tumors) on T‐lymphocyte response to PHA or on NKCA.

The relationships among lipid nutrition, carcinogen‐induced tumorigenesis, and immuno‐logic events is obviously complex. These studies imply that nutritional interventions may have a selective rather than a generalized effect on various immuno competent cell populations. Furthermore, the effects of lipid nutriture, rather than long‐term effects of carcinogen administration, or the presence of bowel tumors appear to play the major role on perceived alterations in in vitro immune function. Thus the effects of these lipid nutritional interventions on DMH‐induced tumorigenesis seem independent of their effects on immune phenomena with the immune probes utilized.     

硒在防治大肠癌中作用的研究

目的：阐明硒在大肠癌发生中的地位及其防治大肠癌的作用机理。方法：包括实验和临床两部分。120只Wistar大鼠以二甲肼（DMH）诱发大肠癌，动物随机分为8组予以不同饮食，处死后尸解，观察各脏器出现肿瘤情况。44例大肠癌患者随机分为治疗组与对照组，观察投药前后血清硒浓度与T淋巴细胞亚群、NK、LAK细胞活性的变化，同时测定35例大肠癌组织和正常大肠组织内硒含量。结果：高脂饮食对DMH的致癌性具有明显的促进作用。硒和钙则有明显阻抑DMH的致癌作用，而且硒对高脂饮食的促癌性也有明显的阻抑作用，锗则未见对DMH的致癌性有任何作用。大肠癌患者血硒水平低于正常值，补硒后血硒明显升高，与对照组差别显著（P＜0．01），治疗组的CD3、CD4、CD4／CD8及NK、LAK细胞活性补硒后有明显升高，与对照组差别显著。此外，大肠癌组织内硒含量明显低于周围大肠组织的硒含量。结论：硒具有阻抑实验性大肠癌发生的作用，补硒具有促进人体细胞免疫的功能，大肠癌的发生则可能与局部低硒以致免疫力降低有关。     

Effect of polyphenolic extracts from red wine and 4–OH–coumaric acid on 1,2–dimethylhydrazine–induced colon carcinogenesis in rats

Summary Background Total polyphenolic extracts from red wine protect against azoxymethane (AOM)–induced colon carcinogenesis in rats. Since red wine contains more than 200 different polyphenolic compounds, it is still unclear which substances are responsible for this effect. Aim of the study We investigated the effect of high molecular weight polyphenols (HMWP), low molecular weight polyphenols (LMWP) and total polyphenolic extracts from red wine (WE) on colon carcinogenesis. We also tested the effect of 4–OH–coumaric acid, a potent phenolic antioxidant present in wine and fruit. Methods F344 rats were treated weekly with 1,2–dimethylhydrazine (DMH) (30 mg/kg b.w. subcutaneously x 10 times). One week after the final DMH injection rats were divided into five groups and fed: a) a high fat (HF) diet containing 23% corn oil (w/w), as control or the same basal diet supplemented with b) 0.11 % (w/w) WE; c) 0.027% (w/w) HMWP d) 0.083% (w/w) LMWP or e) 0.1 % (w/w) 4–OH–coumaric acid. The dietary treatments continued until sacrifice, 16 weeks after the last DMH injection. Results WE treated rats had significantly fewer (p < 0.05) colorectal adenomas than controls, while rats in other treatment groups did not differ significantly from controls (colorectal adenomas/rat were: 2.2 ± 0.3; 1.4 ± 0.2; 2.9 ± 0.5; 2.6 ± 0.4; 2.3 ± 0.3; in controls, WE, HMWP, LMWP and 4–OH–coumaric acid groups, respectively; means ± SE). The mean number of colorectal carcinomas per rat was similar among all experimental groups. Proliferative activity in the normal colon mucosa did not vary among experimental groups. Conclusions Total polyphenolic extracts (WE) from red wine, but neither the HMWP nor the LMWP, have some inhibitory effect on the process of colon carcinogenesis by DMH reducing the number of adenomas.     

T-cell mitogenesis and natural killer cell activity in colonic tumor-bearing and nontumor-bearing rats fed diets high in lipid with and without cholesterol

It has been shown that rats fed diets high in lipid and cholesterol develop more 1,2-dimethylhydrazine (DMH)-induced bowel tumors than those fed diets low in lipid or without cholesterol. To further explore the effects of these dietary regimens on immune function, rats were fed diets containing 20% safflower or coconut oil, with or without cholesterol (1%) and cholic acid (0.3%), for 35 weeks during which time they were given DMH. Only rats bearing one or more colon tumors and that showed no evidence of weight loss were utilized. Two parameters of cell-mediated immune function were assessed in tumor- and nontumor-bearing control rats: a) response to the T-cell mitogen, phytohemaglutinin (PHA), and b) natural killer cell activity (NKCA). Nearly total suppression of PHA response was observed in the polyunsaturated fat diet group compared with the saturated fat diet groups. Addition of cholesterol to either the polyunsaturated or saturated fat diets diminished PHA response and, to a lesser degree, of T-lymphocytes from rats fed these diets. NKCA, however, was unaffected by either the quality of dietary fat or cholesterol. There were no detectable effects of DMH per se 15 weeks after the last injection (or in the presence or absence of tumors) on T-lymphocyte response to PHA or on NKCA. The relationships among lipid nutrition, carcinogen-induced tumorigenesis, and immunologic events is obviously complex. These studies imply that nutritional interventions may have a selective rather than a generalized effect on various immunocompetent cell populations. Furthermore, the effects of lipid nutriture, rather than long-term effects of carcinogen administration, or the presence of bowel tumors appear to play the major role on perceived alterations in in vitro immune function. Thus the effects of these lipid nutritional interventions on DMH-induced tumorigenesis seem independent of their effects on immune phenomena with the immune probes utilized.     

Effect of spices on lipid metabolism in 1,2-dimethylhydrazine-induced rat colon carcinogenesis

Colon cancer is the second most common cancer among men and women worldwide. We investigated the effect of red chilli (Capsicum annum L.), cumin (Cuminum cyminum L.), and black pepper (Piper nigrum L.) on colon cancer induced in rats by a colon-specific carcinogen, 1,2-dimethylhydrazine (DMH). Colon cancer was induced by subcutaneous injection of DMH at a dosage of 20 mg/kg of body weight (15 doses, at 1-week intervals). The rats were continued with the standard pellet diet and supplemented red chilli [C. annum L., 0.015% (wt/wt) mixed with the diet], cumin seeds [C. cyminum L., 1.25% (wt/wt) mixed with the diet], and black pepper (P. nigrum L., 0.5% (wt/wt) mixed with the diet] throughout the experimental period. After the total experimental period of 32 weeks (including 2 weeks of acclimatization) the incidence and number of tumors in the colon were observed to be significantly higher in the rats administered DMH and/or red chillis, as compared with the cumin + DMH and black pepper + DMH groups. No tumors were observed in the control, cumin + DMH, or black pepper + DMH groups. The levels of fecal bile acids and neutral sterols in 24-hour fecal samples were significantly decreased in DMH + chilli-administered rats, while the excretion of fecal bile acids and neutral sterols was significantly increased in cumin + DMH- and black pepper + DMH-administered rats. In DMH-, chilli-, and chilli + DMH-administered rats the levels of cholesterol, cholesterol/phospholipid ratio, and 3-hydroxy-3-methylglutaryl-CoA reductase activity were decreased in cumin + DMH- and black pepper + DMH-treated rats. The phospholipid levels were reduced in the DMH, chilli, and chilli + DMH groups as compared with the cumin + DMH and black pepper + DMH groups. Our results show that chilli supplementation promotes colon carcinogenesis, whereas cumin or black pepper suppresses colon carcinogensis in the presence of the procarcinogen DMH.     

The protective role of Lychnophora ericoides Mart. (Brazilian arnica) in 1,2-dimethylhydrazine-induced experimental colon carcinogenesis

Aberrant crypt foci (ACF) and colon rectal mucosal epithelial cell proliferation have been shown to be increased in patients with colon cancer and have been largely used for early detection of factors that influence colorectal carcinogenesis in rats. Fifty male Wistar rats were randomly divided into 5 groups. The groups G1 to G4 were given 4 injections of the carcinogen 1,2-dimethylhydrazine (DMH). The G2 group received Lychnophora ericoides (LE) extracts for 6 wk. The groups G3 and G4 received LE for 4 wk and 2 wk, respectively, at the postinitiation and initiation phases of colonic carcinogenesis. The group G5 was the control. Forty-two days after the first injections of DMH for the neoplasic induction, we observed a statistically significant decrease in the number of aberrant crypt foci (ACF) and an attenuation of the increase in cell proliferation induced by DMH in all the LE-treated groups. Thus, we concluded that Lychnophora ericoides extracts were effective against the development of cancer. These data suggest that LE has a protective influence on the process of colon carcinogenesis, suppressing both the initiation and the promotion of colonic carcinogenesis.     

魔芋精粉对二甲肼诱发大鼠结肠癌的影响

用二甲肼诱发大鼠结肠癌的同时，于基础饲料中加入５％或１０％魔芋精粉，另设高脂组，观察对发癌率的影响。实验结果表明结肠癌发生率各实验组与阳性组无显著性差异，高脂组显示一定的促癌作用。本实验未观察到魔芋精粉对诱发的实验性肠癌具有抑制作用。     

The Protective Role of Lychnophora ericoides Mart. (Brazilian Arnica) in 1,2-Dimethylhydrazine-Induced Experimental Colon Carcinogenesis

Aberrant crypt foci (ACF) and colon rectal mucosal epithelial cell proliferation have been shown to be increased in patients with colon cancer and have been largely used for early detection of factors that influence colorectal carcinogenesis in rats. Fifty male Wistar rats were randomly divided into 5 groups. The groups G1 to G4 were given 4 injections of the carcinogen 1,2-dimethylhydrazine (DMH). The G2 group received Lychnophora ericoides (LE) extracts for 6 wk. The groups G3 and G4 received LE for 4 wk and 2 wk, respectively, at the postinitiation and initiation phases of colonic carcinogenesis. The group G5 was the control. Forty-two days after the first injections of DMH for the neoplasic induction, we observed a statistically significant decrease in the number of aberrant crypt foci (ACF) and an attenuation of the increase in cell proliferation induced by DMH in all the LE-treated groups. Thus, we concluded that Lychnophora ericoides extracts were effective against the development of cancer. These data suggest that LE has a protective influence on the process of colon carcinogenesis, suppressing both the initiation and the promotion of colonic carcinogenesis.     

A protective role of dietary vitamin D3 in rat colon carcinogenesis

The aim of the present work was to gain insight into a putative anticancer effect of dietary vitamin D3 (cholecalciferol) in a rat model of colon carcinogenesis. Male rats were assigned to three different dietary groups. The dietary regimens were based on a standard murine-defined diet (AIN-76A) or a stress diet containing 20% fat, reduced Ca2+ concentration, a high phosphorus-to-Ca2+ ratio, and either low or high vitamin D3 content. Colorectal cancer was induced by administration of the procarcinogen 1,2-dimethylhydrazine (DMH). Blood Ca2+, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and 25-hydroxyvitamin D3 [25(OH)D3] levels were measured in DMH-treated rats and in respective weight- and age-matched dietary control groups. Colonic epithelial proliferation was assessed by determining thymidine kinase (TK) activity, bromodeoxyuridine (BrdUrd) incorporation into crypt cell DNA, and the mean labeling index along the colonic crypt continuum. Maintenance of rats on the stress diet either unmodified or supplemented with vitamin D3 in the absence of carcinogen treatment provoked a time-dependent rise in colonic TK activity and hyperproliferation of colonic epithelium. DMH treatment of rats maintained on the standard diet caused a marked increase in the proliferative indexes of colonic epithelium and in expansion of the crypt proliferative compartment. TK activity and the crypt mitotic zone were significantly augmented in the animal group fed the stress diet. Supplementary vitamin D3 abrogated the stress diet-enhanced colonic responses to the carcinogenic insult. Colon tumor multiplicity was fourfold higher in animals fed the stress diet than in animals maintained on a standard diet. The marked rise in colonic tumor multiplicity and adenocarcinoma incidence in rats fed the stress diet was obliterated by supplemental dietary vitamin D3. Cumulatively, the present results indicate that dietary vitamin D3 impedes the neoplastic process in murine large intestine and strengthen the view that inappropriate changes in dietary components and micronutrients are contributory determinants of colorectal cancer.