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.