Stevens R H, Loven D P, Osborne J W, Lawson A J
Cancer Lett. 1979 Aug;7(4):227-34. doi: 10.1016/s0304-3835(79)80085-3.
The intracellular concentrations of adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) in 1,2-dimethylhydrazine (DMH) induced rat colon tumors were previously reported to be one-half and twice, respectively, that measured in normal rat colon tissue. The results of this present study indicate that the total amount of cyclic nucleotide hydrolysis by the phosphodiesterase enzymes (PDE) could account for the lower cAMP and elevated cGMP noted in cancer tissue. PDE activities in homogenates prepared from normal and neoplastic tissue showed general similarities in both their hydrogen and metal ion dependencies with optimum degradation of nucleotides occurring at pH 7.2-7.8 in the presence of either Mg2+ or Mn2+ ions. The enzymes from both tissue types were inhibited to a similar extent by papaverine and theophylline. Distribution studies indicated PDE activities were similar throughout the entire length of the normal colon; consequently, the anomalous activities measured in the tumors were attributable to the specific cell population and not to the particular site at which malignancy arose. Thus, the findings of this study suggest that one cause for lowered cAMP and elevated cGMP levels in DMH induced colon adenocarcinomas was the amount of cyclic nucleotide hydrolysis by PDE in the malignant tissue.
先前报道，1,2 - 二甲基肼（DMH）诱导的大鼠结肠肿瘤中，3',5'-环磷酸腺苷（cAMP）和3',5'-环磷酸鸟苷（cGMP）的细胞内浓度分别是正常大鼠结肠组织中测量值的二分之一和两倍。本研究结果表明，磷酸二酯酶（PDE）对环核苷酸的水解总量可能是癌症组织中cAMP降低和cGMP升高的原因。从正常组织和肿瘤组织制备的匀浆中的PDE活性，在对氢离子和金属离子的依赖性方面总体相似，在Mg2+或Mn2+离子存在的情况下，pH 7.2 - 7.8时核苷酸的降解最佳。两种组织类型的酶都受到罂粟碱和茶碱相似程度的抑制。分布研究表明，PDE活性在正常结肠的整个长度上相似；因此，肿瘤中测量到的异常活性归因于特定的细胞群体，而不是恶性肿瘤发生的特定部位。因此，本研究结果表明，DMH诱导的结肠腺癌中cAMP降低和cGMP水平升高的一个原因是恶性组织中PDE对环核苷酸的水解量。
