Tsou K C, Hong D H, Varello M A, Wheeler J E, Giuntoli R, Mangan C E, Mikuta J J
Cancer. 1985 Nov 1;56(9):2340-7. doi: 10.1002/1097-0142(19851101)56:9<2340::aid-cncr2820560936>3.0.co;2-c.
One hundred endometrium specimens have been studied with flow cytometry for DNA analysis (FCDA) and a proliferative enzyme marker, 5'-nucleotide phosphodiesterase (5'-NPD). FCDA data showed that aneuploidy was present in only 5 of 40 cancer specimens. However, with corrected histograms, a higher DNA value was observed in the G2/M (6%) of all cancer compared with noncancer specimens (4%). Thus, FCDA can be a useful diagnostic aid for endometrial cancer. The determination of 5'-NPD was done with a quenching method based on the use of 5'-(5-iodo-3-indoxyl)-thymidine phosphodiester as a substrate and 4',6-diamidino-2-phenylindole for DNA. This method could qualitatively define which population of the cell cycle had a higher enzyme level and also quantitatively gave the enzyme units per cell. It was found that 12.5% of all cancer specimens had 5'-NPD activity in the G0/G1 cells and 87.5% in the S and/or G2/M cells, whereas in the noncancer specimens 5'-NPD was found in 28.5% of the G0/G1 cells and 71.5% of the specimens had 5'-NPD in the S and/or G2/M cells. Furthermore, the concentration of 5'-NPD was found to be five times higher in the G2/M cells of the cancer specimens than that in the noncancer specimens. However, in the hyperplasia specimens, the activity was only two times higher in the same cell cycle fraction than in the normal specimens. The results of this investigation provided for the first time evidence that this exonuclease activity alters in the cell cycle fractions and that a decrease in the enzyme activity in G0/G1 cells and an increase in G2/M cells may be a useful marker for neoplastic development in human endometrial cancer.
对100份子宫内膜标本进行了流式细胞术DNA分析(FCDA)以及增殖酶标志物5'-核苷酸磷酸二酯酶(5'-NPD)的研究。FCDA数据显示,40份癌症标本中仅有5份存在非整倍体。然而,经校正直方图后,与非癌标本(4%)相比,所有癌症标本的G2/M期(6%)观察到更高的DNA值。因此,FCDA可作为子宫内膜癌的一种有用诊断辅助手段。5'-NPD的测定采用基于以5'-(5-碘-3-吲哚基)-胸苷磷酸二酯为底物和4',6-二脒基-2-苯基吲哚用于DNA的猝灭法。该方法能够定性地确定细胞周期的哪个群体具有更高的酶水平,并且还能定量给出每个细胞的酶单位。结果发现,所有癌症标本中12.5%在G0/G1期细胞具有5'-NPD活性,87.5%在S期和/或G2/M期细胞具有该活性,而在非癌标本中,28.5%的G0/G1期细胞具有5'-NPD,71.5%的标本在S期和/或G2/M期细胞具有5'-NPD。此外,发现癌症标本的G2/M期细胞中5'-NPD的浓度比非癌标本高五倍。然而,在增生标本中,相同细胞周期部分的活性仅比正常标本高两倍。本研究结果首次提供了证据,表明这种核酸外切酶活性在细胞周期部分发生改变,并且G0/G1期细胞中酶活性降低而G2/M期细胞中酶活性增加可能是人类子宫内膜癌肿瘤发生发展的一个有用标志物。