Nuclear poly(ADP-ribose) polymerase levels as well as the DNA strand break levels of whole-brain neuronal and astroglial cells were investigated . Three-and 30month-old rats were used . Low-molecular-weight neurofilaments and glutamine synthetase served as neuronal and astroglial markers, respectively . A large increase in the poly(ADP-ribose] polymerase activity was observed in the neurons (threefold) and astrocytes (3 .7-fold) derived from 30-month-old rats . Similarly, the amount of poly(ADP-ribose) polymerase, evaluated per milligram of DNA, in-creased~3 .5-fold in neurons and 3 .9-fold in astrocytes prepared from 30-month-old rats . Whether the increase in the poly(ADP-ribose) polymerase activity was due to an enhanced rate of DNA strand break was investigated by determining the rate of DNA unwinding . A significant increase in DNA unwinding rate was detected in the neurons {2 .7-fold}, although a lower increase was observed in the astroglia (1 .3-fold) of aged animals .

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Poly(ADP-ribose)polymerase, a chromatin-bound enzyme, actively participates in processes such as cell proliferation, differentiation, and DNA repair and replication. This enzyme is also implicated in cell transformation, and its inhibition has been proposed to potentiate anti-cancer drug activity. Since cells prepared from tumor biopsies and established tumor cell lines are commonly used to evaluate the efficiency of anticancer therapies, we have compared poly(ADP-ribose)polymerase activity in animal tumor cells growing in vivo and in cell culture. Three tumor types were tested: a mastocytoma (P815), a lymphoma (RDM4), and a glioma (C6). Our results show that cell culture alters poly(ADP-ribose)polymerase levels and activity. Endogenous poly(ADP-ribose) activity was several fold higher in exponentially growing cells than in cells freshly recovered from solid or ascitic tumors. Moreover, polymerase activity increased with culture time, reaching a maximum when cells became confluent. Measurements of poly(ADP-ribose)polymerase gene expression and protein amount indicate that lower enzyme activity in tumors grown in vivo are sustained by decreases in poly(ADP-ribose)polymerase mRNA and protein amount. In contrast, the increase in endogenous poly(ADP-ribose)polymerase activity observed in cultured cells was due to enzyme activation and not to de novo protein synthesis. Such differences must be considered when assessing the applicability of cell-culture results to in vivo situations.

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