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 <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 < 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 < 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 antipoly(ADP-ribose) antibody supported this view.

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This work was supported in part by Grants-in-Aid for Scientific Research and Cancer Research Fund from the Ministry of Education, Science, and Culture, Japan, and by a research grant from the Vitamin B Research Committee.

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