Kitagawa T, Michalopoulos G, Pitot H C
Cancer Res. 1975 Dec;35(12):3682-92.
The level of unscheduled DNA synthesis in the parenchymal cells from hyperplastic nodules and from the entire liver of rats fed N-2-fluorenylacetamide was studied and compared with that of normal liver cells. Measurements of unscheduled DNA synthesis were carried out by the use of a primary liver cell culture system. Livers were perfused with collagenase, the cells from individual hyperplastic nodules, and/or from the whole liver aspirated and plated onto plastic Petri dishes. Simultaneous histochemical measurements of beta-glucuronidase were carried out in the cultured cells as an aid in distinguishing functional cell types. The cells from hyperplastic nodules obtained from the liver during carcinogen feeding survived much longer than normal liver cells in culture. The level of unscheduled DNA synthesis was determined radioautographically after exposing cells to ultraviolet light and incubating with [3H]thymidine. [3H]Thymidine labeling was variable among individual nodules or animals and fluctuated as a function of the number of days in culture. In general, however, the level of unscheduled DNA synthesis in the cells from hyperplastic nodules was always higher than or similar to that of normal liver cells. Thus, the cells of hyperplastic nodules are not more readily transformed into the malignant state than normal cells as a result of their lowered DNA repair mechanisms.
研究了喂食N-2-芴基乙酰胺的大鼠增生性结节实质细胞和整个肝脏中DNA的非预定合成水平，并与正常肝细胞的该水平进行了比较。使用原代肝细胞培养系统进行DNA非预定合成的测量。用胶原酶灌注肝脏，从单个增生性结节和/或整个肝脏中吸出细胞并接种到塑料培养皿上。在培养细胞中同时进行β-葡萄糖醛酸酶的组织化学测量，以帮助区分功能细胞类型。在致癌物喂养期间从肝脏获得的增生性结节细胞在培养中存活的时间比正常肝细胞长得多。在将细胞暴露于紫外线并用[3H]胸腺嘧啶核苷孵育后，通过放射自显影法测定DNA非预定合成水平。[3H]胸腺嘧啶核苷标记在各个结节或动物之间存在差异，并随培养天数而波动。然而，一般来说，增生性结节细胞中DNA非预定合成水平总是高于或类似于正常肝细胞。因此，增生性结节细胞不会因其降低的DNA修复机制而比正常细胞更容易转化为恶性状态。
