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本文对大鼠肝癌及癌前期肝内TP的底物诱导和激素诱导作了比较研究。在3′-MeDAB诱发的肝癌中,TP活性很低,且不因注射色氨酸或氢可地松而升高,而癌周组织则仍保留对底物和激素诱导的能力。喂3′-MeDAB 13天、28天、90天大鼠肝内TP的底物诱导效应都较对照组为低。急性注射3′-MeDAB25小时,以100毫克/100克体重的L-色氨酸进行诱导,TP的诱导效应亦较对照组为低。氢可地松诱导的结果与底物诱导的相似,无论在喂或急性注射3′-MeDAB的情况下,TP的诱导效应都受到抑制。但在相同条件下,非致癌物,2-MeDAB,对TP的底物诱导和激素诱导(慢性的或急性的实验)也有相似的作用。诱导后肝癌组织或喂偶氮染料的肝组织中都未发现有TP的抑制物或狗尿酸酶的激活物。微粒体及正铁血红素与上清液的加合实验表明:(1)肝癌微粒体几乎完全不具有激活TP的活力;癌前期(3′-MeDAB组)肝微粒体已部分失去此种生化功能,但2-MeDAB组微粒体则否。3′-MeDAB对肝微粒体中辅助因子(正铁血红素)的结构并无破坏,而可能使辅助因子的含量减少。(2)微粒体对激活上清液TP的效果较自由的正铁血红素差,即使加入过量微粒体亦不能使TP活性增高到加入正铁血红素的水平;微粒体对3′-MeDAB组上清液的激活不如对2-MeDAB组及对照组上清液(底物或激素诱导)的激活显著,而正铁血红素对三组上清液都有显著激活。(3)肝癌细胞上清液只合有极少量的TP蛋白,且不因注射色氨酸或氢可地松而增加;癌前期肝细胞上清液的TP蛋白因底物或激素诱导而增加的量都较对照粗低。2-MeDAB组也有相似现象。以上结果表明,肝癌及癌前期肝内TP诱导的受损,主要是由于诱导后TP蛋白的缺少,而不是由于辅助因子(如正铁血红素)的不足,或非酶蛋白的增多。
In this study, we compared the substrate induction and hormone induction of hepatocellular carcinoma in rat liver and precancerous TP. In 3′-MeDAB-induced liver cancer, TP activity is very low and does not increase due to the injection of tryptophan or hydrocortisone, while the tissue of the cancer still retains the ability to induce substrates and hormones. The substrate-inducing effect of intrahepatic TP in rats fed with 3′-MeDAB 13 days, 28 days, and 90 days was lower than that of the control group. Acute injection of 3′-MeDAB for 25 hours was induced with 100 mg/100 g body weight of L-tryptophan, and the induction effect of TP was also lower than that of the control group. The results of induction with hydrocortisone were similar to those induced by the substrate, and the induction effect of TP was suppressed both in the case of feeding or acute injection of 3′-MeDAB. However, under the same conditions, non-carcinogens, 2-MeDAB, have similar effects on substrate induction and hormone induction (chronic or acute experiments) of TP. No inhibitors of TP or uricase activators were found in liver tissue after induction or in liver tissues fed with azo dyes. Addition experiments of microsomes, hemin, and supernatants showed that: (1) Liver microglia almost completely did not have the activity of activating TP; liver microsomes in the precancerous phase (3′-MeDAB group) partially lost this biochemistry. Functional, but not in the 2-MeDAB group microsomes. 3′-MeDAB does not destroy the structure of the cofactor (heme) in liver microsomes, but may reduce the content of cofactors. (2) The effect of microsomes on the activation of supernatant TP was poorer than that of free heme. Even if excess microsomes were added, the activity of TP could not be increased to the level of added heme; microsomes to 3′-MeDAB group. The activation of the supernatant was not as significant as the activation of the supernatant (substrate or hormone induction) in the 2-MeDAB group and the control group, whereas the heme was significantly activated in the three groups of supernatants. (3) The supernatant of hepatocellular carcinoma cells contains only a very small amount of TP protein and does not increase due to the injection of tryptophan or hydrocortisone; the pre-cancerous hepatocyte supernatant TP protein is increased due to substrate or hormone induction. The amount of crude was lower than the control. The 2-MeDAB group also has a similar phenomenon. The above results indicate that the impairment of intrahepatic TP induction in liver cancer and precancerous lesions is mainly due to the lack of TP protein after induction, not to the deficiency of cofactors (such as heme) or the increase of non-enzymatic proteins.