CARCINOGEN-INDUCED ACCUMULATION OF ADENOASSOCIATED PARVOVIRUS DNA IS TRANSIENT AS A RESULT OF 2 ANTAGONISTIC ACTIVITIES THAT BOTH REQUIRE DENOVO PROTEIN-SYNTHESIS

Helper-independent synthesis of adeno-associated parvovirus type 5 (AAV-5) DNA in SV40-transformed Syrian hamster cells is induced by chemical carcinogens, UV light and other stress treatments and has previously been shown to be transient. To gain some insight into the underlying mechanism, the influence of inhibitors of protein synthesis on AAV DNA accumulation was investigated. It is shown that transience is the result of 2 antagonistic activities-synthesis and decomposition. Both depend on de novo protein synthesis and are in part overlapping. The 2 activities are influenced by the amount of AAV uptake and/or by cell density. In less dense cultures, calculated initial amount of AAV DNA and relative accumulation per cell are higher. The effect may be due to the activity of transiently synthesized AAV-encoded regulatory proteins that increase replication and have inhibitory effects on DNA decomposition, or to the influence on cellular adhesion.