mAFP基因转染树突状细胞免疫对小鼠诱发性肝癌发生的影响

目的:探讨用mAFP基因转染的树突状细胞(dendritic cells,DC)瘤苗免疫对小鼠诱发性肝癌发生的影响。方法:诱导、扩增C57BL/6J小鼠DC。将表达小鼠AFP基因(mAFP)的重组腺病毒转染DC。80只C57BL/6J雄性小鼠随机分为A、B、C、D组,每组20只。以单纯DC为A组;将表达mAFP基因的重组腺病毒转染DC(pAd-BM5-mAFP-DCs)为B组;表达mAFP基因的质粒DNA(pAdBM5-mAFP)为C组;以单纯PBS(磷酸缓冲液)注射为对照组D组。免疫方法:实验组在每只小鼠的左胁部注射5×105个细胞(0.1ml/次),连续免疫3天,以后每7天接种疫苗1次,继续免疫4次。正常对照组,仅注射0.1ml PBS。在接种免疫的同时,给以二乙基亚硝胺(DEN)、四氯化碳(CCl4)和乙醇联合诱癌。诱癌20周后处死小鼠,检查成瘤情况。同时对肝脏标本进行组织病理学检查。结果:80只免疫小鼠中,A组肝细胞癌发生率为70%;B组肝细胞癌发生率仅为25%;C组肝癌发生率为65%;D组肝癌发生率为75%。B组与其它对照组比较有显著性差异(p<0.05),其他各组比较无显著性意义。结论:转基因pAdBM5-mAFP-DC瘤苗免疫自然诱癌的C57BL/6J小鼠,能激发较强的抗肿瘤免疫反应,降低肝癌的发生率。     

mAFP基因转染树突状细胞免疫对小鼠诱发性肝癌发生的影响

目的:探讨用mAFP基因转染的树突状细胞(dendritic cells,DC)瘤苗免疫对小鼠诱发性肝癌发生的影响.方法:诱导、扩增C57BL/6J小鼠DC.将表达小鼠AFP基因(mAFP)的重组腺病毒转染DC.80只C57BL/6J雄性小鼠随机分为A、B、C、D组,每组20只.以单纯DC为A组;将表达mAFP基因的重组腺病毒转染DC(pAdBM5-mAFP-DCs)为B组;表达mAFP基因的质粒DNA(pAdBM5-mAFP)为C组;以单纯PBS(磷酸缓冲液)注射为对照组D组.免疫方法:实验组在每只小鼠的左胁部注射5×105个细胞(0.1ml/资),连续免疫3天,以后每7天接种疫苗1次,继续免疫4次.正常对照组,仅注射0.1ml PBS.在接种免疫的同时,给以二乙基亚硝胺(DEN)、四氯化碳(CCl4)和乙醇联合诱癌.诱癌20周后处死小鼠,检查成瘤情况.同时对肝脏标本进行组织病理学检查.结果:80只免疫小鼠中,A组肝细胞癌发生率为70%;B组肝细胞癌发生率仅为25%;C组肝癌发生率为65%;D组肝癌发生率为75%.B组与其它对照组比较有显著性差异(p＜0.05),其他各组比较无显著性意义.结论:转基因pAdBM5-mAFP-DC瘤苗免疫自然诱癌的C57BL/6J小鼠,能激发较强的抗肿瘤免疫反应,降低肝癌的发生率.     

贞芪扶正胶囊对大鼠实验性肝癌发生发展的影响

目的 :观察贞芪扶正胶囊在化学致癌剂二乙基亚硝胺 (diethylnitrosamine ,DENA)诱发大鼠肝癌过程中 ,对肝癌发生、发展的影响。方法 :实验分为 4组 ,除单纯致癌组 (D组 )外 ,其余各组大鼠均在给予致癌剂前 (A组 )、同时 (B组 )或后 (C组 )加给贞芪扶正胶囊。在给予致癌剂 2 0周后取肝脏作肉眼、光镜和电镜检查。结果 :单纯致癌组大鼠均形成肝癌。服用贞芪扶正胶囊的各组情况则有较大差异 ,A组大鼠显示致癌剂对肝脏毒性损伤明显低于其他各组 ,并且当其他各组动物均已形成肝癌甚至已有转移时 ,此组中仅有少数大鼠形成肿瘤 ,多数大鼠则仅出现DENA毒性刺激而形成的细胞增生结节。结论 :贞芪扶正胶囊有预防或延缓肝癌发生的作用     

甲胎蛋白基因转染树突状细胞瘤苗对诱发性小鼠肝癌发生发展的免疫抑制作用

目的 构建小鼠甲胎蛋白(mAFP)基因转染的树突状细胞(DC)瘤苗,评价其在C57BL/6J小鼠自然肝癌诱发过程中的免疫保护作用.方法 诱导、扩增DC.将表达mAFP的重组腺病毒颗粒转染DC,检测转染前后DC细胞表面分子MHC Ⅰ、MHC Ⅱ、CDl8a(LFA)、CD54(ICAM)、CD80(B7.1)和CD86(B7.2)等的变化.80只C57BL/6J雄性小鼠随机分为单纯接种DC组、接种转mAFP基因DC(pAdBM5-mAFP-DC)组、单纯接种重组质粒(pAdBM5-mAFP)组和正常对照组,每组20只.实验组在每只小鼠的左肋部注射5×105个细胞,连续免疫3 d,以后每7 d接种疫苗1次,继续免疫4次;正常对照组仅注射0.1 ml PBS.在接种免疫的同时,给以二乙基亚硝胺(DEN)、四氯化碳(CCl4)和乙醇联合诱癌.诱癌20周后处死小鼠,检查成瘤情况,并对肝脏标本进行组织病理学检查.结果成功构建了转基因pAdBM5-mAFP-DC瘤苗;mAFP基因转染后的DC表面高表达MHC Ⅰ、MHC Ⅱ、CD18a、CD54、CD80和CD86等共刺激分子,其分子表达率分别为69.3%、41.0%、42.1%、63.2%、39.4%和38.6%,与转染前差异有统计学意义(P＜0.05).单纯接种DC组、pAdBM5-mAFPDC组、pAdBM5.mAFP组和正常对照组的肝癌发生率分别为65.0%、25.0%、70.0%和75.0%,pAdBM5-mAFP-DC组与其他组比较,差异有统计学意义(P＜0.05).结论 pAdBM5-mAFP-DC瘤苗免疫自然诱癌的C57BL/6J小鼠,可降低肝癌的发生率,对肝癌的发生有免疫保护作用.     

热休克预处理对瘤苗免疫效果的影响

热休克蛋白(HPS)广泛存在于正常细胞和肿瘤细胞中参与多种细胞内蛋白质的折叠、装配及转运,近年来发现HSP与肿瘤免疫有关,肿瘤组织中HSP肽复合物具有肿瘤疫苗的作用,体外培养条件下热休克处理可诱导H22肝癌细胞表面HSP70的表达,本文探索在H22肝癌疫苗制备过程中热休克预处理是否能增强小鼠H22肝癌细胞瘤苗的免疫效果.实验分组:按瘤菌性质不同实验分为7组,每组小鼠10只,(1)对照组:用生理盐水代替瘤苗免疫小鼠.(2)单纯佐剂组:用脂质体包裹的rIL-2代替瘤苗.(3)无佐剂瘤苗组:用     

间断小剂量DEN诱发大鼠肝癌模型研究

目的:建立实验动物死亡率低、诱癌时间短及与人肝癌的发生过程相似的肝癌模型。方法:取3～4个月龄SD大鼠65只,随机分为两组,实验组大鼠给予0.2%二乙基亚硝胺(diethylnitrosa mine,DEN)灌胃,按体质量10mg/kg给药,每周5次,至14周停药。对照组给予等量生理盐水灌胃。结果:实验组大鼠体质量、一般精神状况均不如对照组,P<0.05。诱癌第14周所有实验组大鼠均诱发出肝细胞性肝癌。结论:间断小剂量给予DEN,可以方便、简单、稳定地建立大鼠肝癌模型。     

饮水微囊藻毒素污染促肝癌作用实验研究

目的 :探讨饮用水低剂量微囊藻毒素对大鼠实验性肝癌形成的促癌作用。方法 :应用二乙基亚硝胺 (DEN)致大鼠肝癌前病变细胞增生灶 (Gamma -谷氨酰转肽酶阳性灶 )发生的短期实验模型研究经饮水摄入低剂量微囊藻毒素的促肝癌作用。结果 :二乙基亚硝胺启动后连续 9周饮用含微囊藻毒素0 5 2 9μg/L的藻培养水 ,大鼠肝Gamma 谷氨酰转肽酶阳性灶数量和面积均出现上升趋势。结论 :长期饮用微囊藻毒素污染的水促肝癌作用不可忽视     

二乙基亚硝胺诱发大鼠肝癌过程中的病理形态观察

 恶性肿瘤的病因和细胞癌变的规律至今尚不完全清楚。我们以往曾对肝癌和皮肤癌进行过初步的实验研究,认为癌变的发生可能与细胞的增生与分化间的平衡失常有关。为了进一步研究癌变的原理,本实验进行了二乙基亚硝胺(DENA)诱发大鼠肝癌过程中肝脏病理形态观察和生化改变的研究。DENA在自然界比较广泛地存在于食物中,可诱发多种动物肿瘤。     

5-脂氧合酶抑制剂齐留通抑制二乙基亚硝胺诱导大鼠肝细胞癌形成的实验研究

目的:研究5-脂氧合酶(5-lipoxygenase,5-LOX)在原发性肝癌中的表达及其抑制剂齐留通对肝癌的影响和机制。方法:实验大鼠随机分为正常对照组(n=5)、模型组(n=8)及齐留通组(n=8)。HE染色观察肝癌病理图片,免疫组织化学染色检测5-LOX蛋白,M2型丙酮酸激酶(M2-PK)与细胞角蛋白19(CK19)的表达,RT-PCR检测肝组织5-LOX的表达,TUNEL检测肝癌细胞凋亡。结果:二乙基亚硝胺(DEN)可以诱导大鼠肝癌模型形成。模型组大鼠肝脏可见中等强度5-LOX的蛋白表达,较对照组明显增强(P<0.01),而齐留通组5-LOX的表达较模型组明显降低(P<0.01)。免疫组织化学检测M2-PK在对照组阴性表达,模型组大鼠中等强度表达(P<0.01),齐留通组弱表达,较模型组差异显著(P<0.05)。CK19在对照组大鼠中阴性表达,模型组大鼠较强表达(P<0.01),齐留通组中等表达,较模型组差异显著(P<0.01)。对照组可检测出5-脂氧合酶mRNA的表达,但明显低于模型组,差异显著(P<0.01);齐留通组的表达介于二者之间,与模型组相比,有统计学意义(P<0.01)。TUNEL法检测对照组几乎未见凋亡细胞,模型组大鼠肝脏仅见少数肝癌细胞阳性表达(30%-50%),而齐留通治疗组大鼠肝脏见大量肝癌细胞阳性表达(70%-80%),与模型组相比有统计学意义(P<0.01)。结论:DEN诱发的大鼠原发性肝癌存在5-脂氧合酶表达,5-脂氧合酶抑制剂可防治DEN诱发的大鼠原发性肝癌的形成,其机制与诱导肝癌细胞凋亡相关。     

贞芪扶正胶囊对大鼠实验性肝癌发生发展的影响

目的：观察贞芪扶正胶囊在化学致癌剂二乙基亚硝胺（diethylnitrosamine,DENA)诱发大鼠肝癌过程中，对肝癌发生、发展的影响。方法；实验分为4组，除单纯致癌组（D组）外，其余各组大鼠均在给予致癌剂前（A组），同时（B组）或后（C组）加给贞芪扶正胶囊，在给予致癌剂20周后取肝脏作肉眼、光镜和电镜检查。结果：单纯致癌组大鼠均形成肝癌。服用贞芪扶正胶囊的各组情况则有较大差异，A组大鼠显示致癌剂对肝脏毒性损伤明显低于其他各组，并且当其他各组动物均已形成肝癌甚至已有转移时，此组中仅有少数大鼠形成肿瘤，多数大鼠则仅出现DENA毒性刺激而形成的细胞增生结节。结论：贞芪扶正胶囊有预防或延缓肝癌发生的作用。     

INHIBITORY EFFECT OF BOSCHNIAKIA ROSSICA ON DEN-INDUCED PRECANCEROUS HEPATIC FOCI AND ITS ANTIOXIDATIVE ACTIVITIES IN RATS

BoschnikiarossicaFedtsch.etFlerovisaparasiticplantgr0wingonther0otofAlnusplants(BetUlaceae).[']Itisoneofthevaluablemedicinalplantsgr0wingonChangbaiMountainareas,itgrowsgreatlyontheChangbaiMountainatl45orl8O0metersabovesealevel,Jilin,China.Itisals0gr0wsintheDemocraticPeople'sRepublicofKorea(DPRK),JaPanandRussian.Boschiakiarossicawasnamed"BuLaoCa0"(antisenilityplant),becauseithastheeffectsoftonifyingthekidneyandstrengtheningYang,andhasbeenusedasatonicinChina.Weis0latedfouririd0idc0mP…     

珍珠梅提取物对二乙基亚硝胺所致大鼠肝脏癌前病变的抑制作用及抗氧化活力的影响

目的研究珍珠梅对二乙基亚硝胺致大鼠肝脏癌前病变灶及抗氧化活力的抑制作用.方法75只大鼠随机分为A、B、C 3组对照组、模型组和治疗组,每组25只.按略改良的Solt-Farber氏方法制作大鼠肝脏癌前病变模型,用珍珠梅提取物饲养大鼠6周后处死,通过免疫组织化学检测癌前病变组织谷胱甘肽S-转移酶(GST-P)和p53蛋白的表达,放射免疫法检测血清肿瘤坏死因子(TNF-α)的含量,比色分析法检测血清、肝线粒体超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活性及丙二醛(MDA)的含量.结果B和C组GST-P的表达率为86.7%和28.6%,p53的表达率为56%和36%,差异均有显著意义,P<0.05;B组血清TNF-α的含量与C组比较,差异有显著意义,P<0.05;B组血清、肝线粒体SOD、GSHPx活性及MDA含量与C组比较,差异均有显著意义,P<0.05.结论珍珠梅提取物对DEN所致大鼠癌前病变灶有抑制作用,可诱发TNF-α的生成,并有抗氧化作用.     

Inhibitory effect of boschniakia rossica on den-induced precancerous hepatic foci and its antioxidative activities in rats

Objective: To investigate the inhibitory effect of Boschniakia rossica (BR) on rat precancerous hepatic foci induced by diethylnitrosamine (DEN) and its antioxidative activities. Methods: The expression of tumor marker—placental form glutathione S-transferase (GST-P), p53 and p21 protein were investigated by immunohistochemistry techniques using ABC method. TNF-α was measured by ELISA and antioxidative activities of SOD, MDA, GSH-Px, GST and CAT were investigated by colorimetric method in rat serum and mitochondria of liver cells. Results: The 500 mg/kg of BR-H₂O extract fraction from BR-methanol extract had inhibitory effect on the formation of DEN-induced GST-P-positive foci in rat liver and the expression of mutant p53 and p21 protein was lower than that of hepatic precancerous lesions. The serum TNF-α was increased by the administration of BR extract in the early stage of chemical hepatocarcinogenesis in rat livers. The serum and liver cells mitochondria activities of SOD and GSH-Px rose again in rats administered with BR-H₂O extract and the increasing activity of GST and content of MDA in the hepatic precancerous were decreased by the BH-H₂O extract. Conclusion: These results indicated that BR-H₂O extract has inhibitory effect on DEN-induced precancerous hepatic foci in rats and induced TNF-α production in rats. The antioxidative action was exhibited by the administration of BR-H₂O extract in the early stage of chemical hepatocarcinogenesis in rat livers. This work was supported by a grant from the National Natural Science Foundation of China (No. 39660021).     

Reduction of hepatocarcinogenesis by ursodeoxycholic acid in rats

Ursodeoxycholic acid (UDCA) is used worldwide for treatment of primary biliary cirrhosis and chronic liver diseases. However, its action on hepatocarcinogenesis remains to be explored. To clarify its effect, in vivo and in vitro experiments were performed. Ninety Fisher 344 rats were fed a standard diet (Group 1, n = 30), a standard diet supplemented with 0.1% UDCA (Group 2, n = 30) and 0.3% UDCA (Group 3, n = 30). The rats were given an i.p. injection of diethylnitrosamine (DEN) weekly for 6 weeks. Fifteen additional rats were fed 0.3% UDCA supplemented diet without DEN treatment (Group 4). The rats were killed at 5, 10 and 18 weeks after the last injection of DEN. The number of liver tumor and percentage of the GST-P-positive hepatocytes were significantly reduced by UDCA treatment. The PCNA-positive cells were decreased by administration of UDCA at 18 weeks. The increased number of apoptotic cells was observed in the GST-P-negative area at 5, 10 and 18 weeks and in the GST-P-positive area at 18 weeks in the UDCA group. Expression of Bax in mitochondria and cytochrome c in cytosol was increased by UDCA treatment. Caspase 3 activity was also increased in the UDCA groups. The addition of UDCA into the culture of Huh7 and Fao hepatocellular carcinoma (HCC) cells induced apoptosis in a dose-dependent manner. The data of the present study suggest that UDCA treatment reduces hepatocarcinogenesis via inducing apoptosis of 'initiated hepatocytes' as well as inhibiting proliferation.     

Cleistocalyx nervosum Extract Ameliorates Chemical-Induced Oxidative Stress in Early Stages of Rat Hepatocarcinogenesis

Purpose: To study the effect of Cleistocalyx nervosum extract (CE) on diethylnitrosamine (DEN) andphenobarbital (PB) induced oxidative stress in early stages of rat hepatocarcinogenesis. Materials and Methods:Male Wistar rats were divided into 4 groups, with Group 1 as a negative control and Group 2 was a positivecontrol receiving DEN injections once a week and PB in drinking water for 6 weeks. Two weeks before DENinitiation and PB treatment, Groups 3 and 4, were fed with 500 and 1000 mg/kg of CEs, respectively, for 8weeks. Results: A number of GST-P-positive foci, preneoplastic lesions, in the liver were markedly increased incarcinogen administered rats, but was comparatively decreased in rats treated with 1000 mg/kg of CE. The CEreduced malondialdehyde in serum and in the livers of rats treated with DEN and PB. Moreover, CE significantlyincreased the activities of glutathione peroxidase and catalase in rat liver. Conclusions: CE appeared to exertits chemopreventive effects by modulating antioxidant status during DEN and PB induced early stages ofhepatocarcinogenesis in rats.     

Decreased expression of Bcl-x protein during hepatocarcinogenesis induced exogenously and endogenously in rats.

Dysregulations of apoptosis have been widely recognized as important events in multi-stage carcinogenesis. Bcl-x, a member of the Bcl-2 family, is known to act as a regulator of apoptosis. The present study was conducted to assess the role of altered Bcl-x protein expression in exogenous and endogenous hepatocarcinogenesis in rats. In the short-term exogenous models, male Fischer 344 rats, 6 weeks old, were given a single intraperitoneal injection of diethylnitrosamine (DEN) at a dose of 200 mg / kg body weight, partially hepatectomized at the end of week 3, administered phenobarbital at a concentration of 0.05% from the end of week 2 for 6 weeks, and sacrificed. In the livers, glutathione S-transferase (GST-P)-positive, putative preneoplastic lesions were induced, and Bcl-x protein expression was decreased in 24.7% of such lesions. The incidence of GST-P-positive lesions with decreased Bcl-x increased depending on the size of the lesions; 18.9%, 32.4% and 86.5% in the lesions smaller than 0.03, between 0.03 and 0.3, and larger than 0.3 mm(2), respectively. In GST-P-positive lesions larger than 0.3 mm(2), both apoptosis induction and cell proliferation activity were enhanced when Bcl-x protein expression was decreased. In the long-term exogenous models, rats were given 10 mg / kg of DEN, partially hepatectomized 4 h after treatment, administered 0.5 mg / kg of colchicine at the end of days 1 and 3, subjected to a selection procedure, and sacrificed at the end of week 45. Hepatocellular carcinomas were induced with the decreased Bcl-x protein expression. In the endogenous model, rats were fed a choline-deficient, L-amino acid-defined diet for 16 or 80 weeks and sacrificed. Bcl-x protein expression was decreased both in GST-P-positive lesions and hepatocellular carcinoma. These results suggest that this decrease of Bcl-x protein might serve as an indicator of the advanced form of preneoplastic lesions, and that this decrease could also be associated with a potential to progress into carcinoma in both exogenous and endogenous hepatocarcinogenesis of rats.     

Inhibition by phenobarbital and lack of effect of amobarbital on the development of liver tumors induced by N-nitrosodiethylamine in juvenile B6C3F1 mice

The effects of phenobarbital (PB) and amobarbital (AB) on the rate of development of hepatocarcinogenesis induced by N-nitrosodiethylamine (DEN) were studied in mice. Groups of 40 B6C3F1 male mice were injected i.p. at 15 days of age with 5 micrograms DEN/g body wt. Beginning at 4 weeks of age, DEN treated groups were given either normal drinking water or water containing either 0.05% PB or AB for up to 36 weeks. DEN alone induced multiple focal hepatic lesions including hepatocellular foci, hepatocellular adenomas and trabecular carcinomas. Subsequent exposure to PB had a suppressing effect on DEN-induced hepatocarcinogenesis. Hepatocellular foci in PB-exposed mice were significantly smaller in size (area) and fewer in number throughout the study. Also, PB treatment either prolonged the latency period or significantly slowed the rate at which hepatocellular tumors developed in these mice. No such effects were seen in AB-exposed mice; AB neither inhibited nor promoted the development of focal hepatic lesions in DEN-pretreated mice. Possible mechanisms responsible for the inhibition of DEN-induced hepatocarcinogenesis include the feminizing effects of perinatal administration of PB.     

An acyclic retinoid, NIK-333, inhibits N-diethylnitrosamine-induced rat hepatocarcinogenesis through suppression of TGF-alpha expression and cell proliferation

The present study was designed to determine the effects of NIK-333, a synthetic acyclic retinoid, on N-diethylnitrosamine (DEN)-induced hepatocarcinogenesis in male F344 rats. Animals were given DEN dissolved in drinking water at a concentration of 40 p.p.m. for 5 weeks and then provided with drinking water free of DEN for 15 weeks to induce hepatocellular neoplasms. NIK-333 was administered orally (once a day) to rats at doses of 10, 40 and 80 mg/kg body wt for 14 weeks, starting 1 week after the completion of administration of DEN. At 20 weeks after the start of DEN administration, histopathological evaluation was carried out on all animals. The effects of NIK-333 on the cell proliferation activity of non-tumorous areas and liver tumor cells and the immunohistochemical expression of transforming growth factor-alpha (TGF-alpha) were also evaluated. NIK-333 at 40 and 80 mg/kg body wt significantly inhibited hepatocarcinogenesis (P < 0.05). In addition, NIK-333 at the same doses decreased DEN-induced overexpression of TGF-alpha in hepatocellular neoplasms (adenomas and carcinomas) and their surrounding tissue. Furthermore, NIK-333 significantly inhibited cell proliferation activity in the lesions and in non-tumorous areas (P < 0.01). Our results suggest that NIK-333 inhibits DEN-induced hepatocarcinogenesis through suppression of TGF-alpha expression and cell proliferation.     

Decreased Expression of Bcl-x Protein during Hepatocarcinogenesis Induced Exogenously and Endogenously in Rats

Dysregulations of apoptosis have been widely recognized as important events in multi‐stage carcinogenesis. Bcl‐x, a member of the Bcl‐2 family, is known to act as a regulator of apoptosis. The present study was conducted to assess the role of altered Bcl‐x protein expression in exogenous and endogenous hepatocarcinogenesis in rats. In the short‐term exogenous models, male Fischer 344 rats, 6 weeks old, were given a single intraperitoneal injection of diethylnitrosamine (DEN) at a dose of 200 mg/kg body weight, partially hepatectomized at the end of week 3, administered phenobarbital at a concentration of 0.05% from the end of week 2 for 6 weeks, and sacrificed. In the livers, glutathione S‐transferase (GST‐P)‐positive, putative preneoplastic lesions were induced, and Bcl‐x protein expression was decreased in 24.7% of such lesions. The incidence of GST‐P‐positive lesions with decreased Bcl‐x increased depending on the size of the lesions; 18.9%, 32.4% and 86.5% in the lesions smaller than 0.03, between 0.03 and 0.3, and larger than 0.3 mm², respectively. In GST‐P‐positive lesions larger than 0.3 mm², both apoptosis induction and cell proliferation activity were enhanced when Bcl‐x protein expression was decreased. In the long‐term exogenous models, rats were given 10 mg/kg of DEN, partially hepatectomized 4 h after treatment, administered 0.5 mg/kg of colchicine at the end of days 1 and 3, subjected to a selection procedure, and sacrificed at the end of week 45. Hepatocellular carcinomas were induced with the decreased Bcl‐x protein expression. In the endogenous model, rats were fed a choline‐deficient, l ‐amino acid‐defined diet for 16 or 80 weeks and sacrificed. Bcl‐x protein expression was decreased both in GST‐P‐positive lesions and hepatocellular carcinoma. These results suggest that this decrease of Bcl‐x protein might serve as an indicator of the advanced form of preneoplastic lesions, and that this decrease could also be associated with a potential to progress into carcinoma in both exogenous and endogenous hepatocarcinogenesis of rats.