BIOCHEMICAL CHARACTERIZATION OF STAGES OF HEPATOCARCINOGENESIS AFTER A SINGLE DOSE OF DIETHYLNITROSAMINE
BIOCHEMICAL CHARACTERIZATION OF STAGES OF HEPATOCARCINOGENESIS AFTER A SINGLE DOSE OF DIETHYLNITROSAMINE
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DOI：
10.1038/271456a0
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发表时间：
1978-01-01
期刊：
影响因子：
64.8
通讯作者：
KITAGAWA, T
中科院分区：
文献类型：
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作者：
PITOT, HC;BARSNESS, L;KITAGAWA, T
目前对瘤形成的发病机理的理解主要依赖于证明1 - 3，即碳氢化合物诱导小鼠皮肤癌可分为至少两个阶段。有证据表明，在非表皮组织癌变的自然史中存在类似的阶段4 -7。例如，Perainoet al.6已经表明，大鼠短期喂食乙酰氨基芴，然后长期喂食含0.05%苯巴比妥的饲料，导致肝癌发生率为100%，而接受乙酰氨基芴且未服用苯巴比妥的动物发生肝癌的几率降低了10倍。Peraino的程序和Kitagawaet等人7的程序，他们先给大鼠喂偶氮染料，然后喂苯巴比妥，要求给大鼠喂致癌物3-8周。另一方面，谢勒和Emmelot 8表明，在部分肝切除术后24小时内给予大鼠单次大剂量二乙基亚硝胺可诱发肝细胞癌，而以相同方式给予低剂量（< 30 mg kg−1）仅引起ATP酶缺陷细胞的小病灶，与之前描述的情况相当9，10。此外，Solt和Farber 11报道，单次给予二乙基亚硝胺，随后给予乙酰氨基芴并进行部分肝切除术，可迅速产生含有γ-谷氨酰转肽酶的病灶，而正常肝脏中则没有该酶的组织化学活性。通过将谢勒和埃默洛特8的方法与Perainoet等6的方法相结合，我们已经能够清楚地区分大鼠肝癌发生的两个阶段。
CURRENT understanding of the pathogenesis of neoplasia rests principally on the demonstration1–3that the induction of carcinomas of mouse skin by hydrocarbons can be separated into at least two stages. There is evidence of similar stages in the natural history of carcinogenesis of nonepidermal tissues4–7. For example, Perainoet al.6have shown that short term feeding of acetylaminofluorene to rats followed by a long term diet containing 0.05% phenobarbital results in 100% incidence of hepatomas, whereas animals receiving acetylaminofluorene and no phenobarbital developed 10 times fewer hepatocarcinomas. Peraino's procedure and that of Kitagawaet al.7, who fed rats azo dye followed by phenobarbital, required that the carcinogen be fed to the rats for 3–8 weeks. On the other hand, Scherer and Emmelot8have shown that a single large dose of diethylnitrosamine given to rats within 24 h of partial hepatectomy can induce hepatocellular carcinomas, whereas low doses (< 30 mg kg−1), given in the same way, give rise only to small foci of cells deficient in ATPase, comparable with those described earlier9,10. Further, Solt and Farber11have reported that a single dose of diethylnitrosamine followed by acetylaminofluorene and partial hepatectomy rapidly produces foci containingγ-glutamyl transpeptidase, in contrast to the situation in normal liver which exhibits no histochemical activity of that enzyme. By combining the procedure of Scherer and Emmelot8with that of Perainoet al.6, we have been able to distinguish clearly between two stages in the genesis of liver cancer in rats.