物理、化学因子诱癌模型及其剂量-效应相关模式

目的 建立由物理因子诱发的骨肉瘤动物模型和瘤细胞模型 ,以及由化学因子诱发的肺癌动物模型 ,并研究其剂量 效应相关模式。方法 用放射性超铀核素2 3 8钚作为物理致癌因子在大鼠体内诱发骨肉瘤 ;从瘤组织中分离出瘤细胞系并研究其移植诱癌毒力用二苯并 [a ,h]蒽作为化学致癌因子 ,在小鼠体内诱发肺癌。研究上述两种致癌因子的剂量 效应相关模式。结果 上述两种致癌因子的剂量 效应相关模式都符合线性平方模型。

舌癌动物模型的建立与研究进展

口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)是口腔癌中恶性程度比较高的癌症之一,发生部位有舌、颊部、口底及咽部等。在口腔鳞癌中目前发病率最高的又为舌鳞状细胞癌(oral tongue squamous cell carcinoma,OTSCC),舌癌的发生严重影响患者的语言、吞咽等相关功能,甚至危害患者的生命,所以舌癌一旦发现要及早地治疗。舌癌的致病因素具有多样化的特点,具体发病机制一直是国内外学者共同探究的问题。因此,建立舌癌动物模型是对肿瘤发病机制及预防和治疗研究的一个重要前提。本文就近年来舌癌动物模型建立方法作一综述。

芳维A酸乙酯对7,12-二甲基苯蒽/巴豆油诱发小鼠皮肤乳头状瘤消退作用的研究

应用 7， 12-二甲基苯蒽 /巴豆油二阶段诱癌法诱发小鼠皮肤乳头状瘤，观察口服芳维 A酸乙酯 14天的消退作用，利用原位 DNA末端标记技术 (TUNEL法 )和电镜检查结合计算机图像分析对表皮细胞凋亡进行检测。结果，在第 14天，对照组和各服药组小鼠皮肤乳头状瘤平均直径增殖率分别为 125.3％、 66.7％、 79.2％、 91.6％；细胞凋亡指数分别为： 2.3％、 37.7％、 32.3％、 20.5％；服药组与对照组有显著性差异 (P< 0.001)，其消退作用与剂量呈依赖关系，并与细胞凋亡程度正相关 (r=0.89)。结果表明，芳维 A酸乙酯对 DMBA/巴豆油诱发的小鼠皮肤乳头状瘤有明显的消退作用，其作用与诱导异常增殖表皮细胞凋亡有关。

Progression of diethylnitrosamine-induced hepatic carcinogenesis in carnitine-depleted rats

AIM:To investigate whether carnitine deficiency is a risk factor during the development of diethylnitrosamine (DENA)-induced hepatic carcinogenesis. METHODS:A total of 60 male Wistar albino rats were divided into six groups with 10 animals in each group.Rats in group 1(control group)received a single intraperitoneal(i.p.)injection of normal saline. Animals in group 2(carnitine-supplemented group) were given L-carnitine(200 mg/kg per day)in drinking water for 8 wk.Animals in group 3(carnitine-depleted group)were given D-carnitine(200 mg/kg per day)and mildronate(200 mg/kg per day)in drinking water for 8 wk.Rats in group 4(DENA group)were injected with a single dose of DENA(200 mg/kg,i.p.)and 2 wk later received a single dose of carbon tetrachloride(2 mL/kg) by gavage as 1:1 dilution in corn oil.Animals in group 5(DENA-carnitine depleted group)received the same treatment as group 3 and group 4.Rats in group 6 (DENA-carnitine supplemented group)received the same treatment as group 2 and group 4.RESULTS:Administration of DENA resulted in a significant increase in alanine transaminase(ALT), gamma-glutamyl transferase(G-GT),alkaline phosphatase(ALP),total bilirubin,thiobarbituric acid reactive substances(TBARS)and total nitrate/ nitrite(NOx)and a significant decrease in reduced glutathione(GSH),glutathione peroxidase(GSHPx), catalase(CAT)and total carnitine content in liver tissues.In the carnitine-depleted rat model,DENA induced a dramatic increase in serum ALT,G-GT,ALP and total bilirubin,as well as a progressive reduction in total carnitine content in liver tissues.Interestingly, L-carnitine supplementation resulted in a complete reversal of the increase in liver enzymes,TBARS and NOx,and a decrease in total carnitine,GSH,GSHPx, and CAT induced by DENA,compared with the control values.Histopathological examination of liver tissues confirmed the biochemical data,where L-carnitine prevented DENA-induced hepatic carcinogenesis while D-carnitine-mildronate aggravated DENA-induced hepatic damage. CONCLUSION:Data from this study suggest for the first time that:(1)carnitine deficiency is a risk factor and should be viewed as a mechanism in DENA- induced hepatic carcinogenesis;(2)oxidative stress plays an important role but is not the only cause of DENA-induced hepatic carcinogenesis;and(3) long-term L-carnitine supplementation prevents the development of DENA-induced liver cancer.