Shetty T K, Narurkar L M, Narurkar M V
Br J Cancer. 1971 Mar;25(1):109-20. doi: 10.1038/bjc.1971.16.
Cytoplasmic changes were investigated in livers of rats at various intervals up to 50 weeks during primary induction of hepatoma by thioacetamide feeding.Microsomal Glucose-6-phosphatase and ATPase activities were shown to decrease progressively with increased period of thioacetamide feeding the fall in activities being more pronounced during the first 15 weeks.Hormonal induction of tryptophan pyrrolase and tyrosine transaminase activities was shown to undergo a significant decrease of 65% and 55% respectively at the end of 50 weeks feeding.The substrate induced tryptophan pyrrolase activity was decreased to 50% during the 50 weeks period whereas the substrate induced tyrosine transaminase activity gradually increased to 200%. The latter is attributable to differences in the optimal induction dose of tyrosine in normal and carcinogen fed rats.The m-RNA template lifetime for tryptophan pyrrolase was shown to be exceeding 24 hours in normal rats as against that of 13 hours in rats fed with carcinogen for 30 weeks. On the other hand the m-RNA template lifetime for tyrosine transaminase was 3 hours in control rats while it was 7 hours in the carcinogen fed rats.The observed changes were shown to occur long before the onset of malignant transformation.The alterations in terms of decreased Glucose-6-phosphatase and substrate induced tryptophan pyrrolase activities were shown to be reversible when the carcinogen was withdrawn from the diet after 30 weeks of feeding.The significance of these observations is discussed in relation to damage to endoplasmic reticulum during hepatocarcinogenesis.
通过喂食硫代乙酰胺对大鼠进行肝癌初级诱导期间，在长达50周的不同时间间隔对大鼠肝脏中的细胞质变化进行了研究。结果显示，微粒体葡萄糖-6-磷酸酶和ATP酶活性随着硫代乙酰胺喂食时间的延长而逐渐降低，在前15周活性下降更为明显。在喂食50周结束时，色氨酸吡咯酶和酪氨酸转氨酶活性的激素诱导分别显著下降了65%和55%。在50周期间，底物诱导的色氨酸吡咯酶活性降至50%，而底物诱导的酪氨酸转氨酶活性逐渐增加至200%。后者归因于正常大鼠和喂食致癌物大鼠中酪氨酸最佳诱导剂量的差异。正常大鼠中色氨酸吡咯酶的mRNA模板寿命超过24小时，而喂食致癌物30周的大鼠中为13小时。另一方面，对照大鼠中酪氨酸转氨酶的mRNA模板寿命为3小时，而喂食致癌物的大鼠中为7小时。观察到的这些变化早在恶性转化开始之前就已发生。当在喂食30周后从饮食中去除致癌物时，葡萄糖-6-磷酸酶和底物诱导的色氨酸吡咯酶活性降低方面的改变显示是可逆的。结合肝癌发生过程中内质网的损伤对这些观察结果的意义进行了讨论。
