Kitagawa T, Pitot H C
Cancer Res. 1975 Apr;35(4):1075-84.
Changes in the levels of serine dehydratase and glucose-6-phosphatase induced by dietary stimuli or starvation in hyperplastic nodules of rat liver during diethylnitrosamine or N-2-fluorenylacetamide feeding were studied by immuno- and enzyme histochemical methods. The study was performed during carcinogenesis through a combined method of enzyme histochemistry and radioautography. Serine dehydratase was observed diffusely in the cytoplasm of the original hepatocytes in the periportal zone and was induced markedly during diethynitrosamine feeding but only slightly during N-2-fluorenylacetamide feeding. The enzyme was deficient and not inducible in hyperplastic nodules during their developing phase. Later during the feeding period, however, there was an elevation of the level of serine dehydratase and its inducibility with time in the majority of the nodules. A good correlation was observed between serine dehydratase and glucose-6-phosphatase in their elevated levels and response to enviornmental stimuli. There was a minor group of hyperplastic nodules in which the deficiencies of these enzymes persisted and enzyme induction was not observed. A greater number of hyperplastic nodules with persistent enzyme deficiency was seen during diethylnitrosamine carcinogenesis. These results provide further information about the changing biological nature of hyperplastic nodules with respect to their metabolic adaptability and enzyme levels during hepatocarcinogenesis.
采用免疫组织化学和酶组织化学方法,研究了在二乙基亚硝胺或N-2-芴基乙酰胺喂养期间,饮食刺激或饥饿对大鼠肝脏增生性结节中丝氨酸脱水酶和葡萄糖-6-磷酸酶水平的影响。本研究是在致癌过程中通过酶组织化学和放射自显影相结合的方法进行的。丝氨酸脱水酶在门周区原始肝细胞的细胞质中弥漫性观察到,在二乙基亚硝胺喂养期间显著诱导,但在N-2-芴基乙酰胺喂养期间仅轻微诱导。在增生性结节的发育阶段,该酶缺乏且不可诱导。然而,在喂养后期,大多数结节中丝氨酸脱水酶水平升高,且其诱导性随时间增加。丝氨酸脱水酶和葡萄糖-6-磷酸酶在其升高水平和对环境刺激的反应方面存在良好的相关性。有一小群增生性结节,其中这些酶的缺乏持续存在,未观察到酶诱导。在二乙基亚硝胺致癌过程中,可见更多具有持续酶缺乏的增生性结节。这些结果为增生性结节在肝癌发生过程中代谢适应性和酶水平方面不断变化的生物学特性提供了进一步的信息。