Hirai K, Ueda K, Hayaishi O
Cancer Res. 1983 Jul;43(7):3441-6.
The activities of three principal enzymes engaged in the biosynthesis and degradation of poly(adenosine diphosphate-ribose) [poly(ADP-ribose)] were examined in cell nuclei isolated from adenomatous polyps (tubular adenomas of familial polyposis coli, villous adenoma, and tubulovillous adenoma), cancers, and normal mucosa of human colon. The activities of poly(ADP-ribose) synthetase in adenomatous polyps [161 +/- 46 (S.E.) pmol/min/mg DNA] and cancers (114 +/- 32 pmol/min/mg DNA) were, on an average, about 3 and 2 times, respectively, higher than those in normal mucosa (52 +/- 24 pmol/min/mg DNA); the difference was statistically significant (p less than 0.001). The activity of poly(ADP-ribose) glycohydrolase was also significantly high in adenomatous polyps (13.0 +/- 3.4 nmol/min/mg DNA), but not in cancers (10.1 +/- 2.5 nmol/min/mg DNA), compared with normal mucosa (5.2 +/- 1.4 nmol/min/mg DNA) (p less than 0.001). The activity of ADP-ribosyl protein lyase, in contrast, was lower in adenomatous polyps (152 +/- 40 pmol/min/mg DNA) than in normal mucosa (345 +/- 111 pmol/min/mg DNA) and cancers (288 +/- 80 pmol/min/mg DNA) (p less than 0.001). Analyses of reaction products with snake venom phosphodiesterase digestion revealed that poly(ADP-ribose) synthesized in nuclei of normal mucosa, adenomatous polyps, and cancers had the average chain lengths of 2.9, 1.7, and 9.7 ADP-ribose units, respectively. Based upon these values and total amounts of ADP-ribose incorporated, the amount of poly(ADP-ribose) synthesized per mg DNA in 30 min was calculated as 308, 1510, and 106 pmol in the above three types of colon tissues, respectively. These results suggested that a larger amount of monomers and short oligomers of ADP-ribose was synthesized in adenomatous polyps, while a smaller number of longer polymers was produced in cancers as compared with normal mucosa. Immunohistochemical analysis of these tissues using anti-poly(ADP-ribose) antibody supported this view.
对从人结肠的腺瘤性息肉（家族性结肠息肉病的管状腺瘤、绒毛状腺瘤和管状绒毛状腺瘤）、癌症组织以及正常黏膜中分离出的细胞核，检测了参与聚（腺苷二磷酸核糖）[聚（ADP - 核糖）]生物合成和降解的三种主要酶的活性。腺瘤性息肉[161±46（标准误）pmol/分钟/毫克DNA]和癌症组织（114±32 pmol/分钟/毫克DNA）中聚（ADP - 核糖）合成酶的活性，平均分别约为正常黏膜（52±24 pmol/分钟/毫克DNA）中的3倍和2倍；差异具有统计学意义（p＜0.001）。与正常黏膜（5.2±1.4 nmol/分钟/毫克DNA）相比，腺瘤性息肉中聚（ADP - 核糖）糖苷水解酶的活性也显著较高（13.0±3.4 nmol/分钟/毫克DNA），但癌症组织中该酶活性不高（10.1±2.5 nmol/分钟/毫克DNA）（p＜0.001）。相比之下，ADP - 核糖基蛋白裂解酶的活性在腺瘤性息肉中（152±能40 pmol/分钟/毫克DNA）低于正常黏膜（345±111 pmol/分钟/毫克DNA）和癌症组织（288±80 pmol/分钟/毫克DNA）（p＜0.001）。用蛇毒磷酸二酯酶消化反应产物的分析表明，正常黏膜、腺瘤性息肉和癌症组织细胞核中合成的聚（ADP - 核糖）的平均链长分别为2.9、1.7和9.7个ADP - 核糖单位。根据这些数值以及掺入的ADP - 核糖总量，计算出上述三种结肠组织中每毫克DNA在30分钟内合成的聚（ADP - 核糖）量分别为308、1510和106 pmol。这些结果表明，与正常黏膜相比，腺瘤性息肉中合成的ADP - 核糖单体和短寡聚物较多，而癌症组织中产生的较长聚合物较少。使用抗聚（ADP - 核糖）抗体对这些组织进行免疫组织化学分析支持了这一观点。
