DNA amplification of adeno-associated virus as a response to cellular genotoxic stress.
We studied DNA amplification of helper virus-dependent parvoviruses [adeno-associated virus (AAV)] following genotoxic treatment of a number of mammalian cell lines from different species including primary, immortalized, and tumorigenic cells. All cell lines, either infected with AAV or transfected with parvoviral DNA, readily amplified AAV DNA in the absence of helper virus following treatment of cells with a wide variety of genotoxic agents like chemical carcinogens, UV, heat shock, and metabolic inhibitors of DNA replication or protein synthesis. In addition, we show that in the SV40-transformed Chinese hamster cell lines CO60 and CO631 carcinogen-induced AAV DNA amplification may result in a complete AAV replication cycle giving rise to infectious AAV progeny. Our results demonstrate that AAV DNA amplification induced by genotoxic agents is completely independent of the presence of viral helper functions. Because its induction is not restricted to a specific cell type or to a malignant phenotype, AAV DNA amplification may represent a marker for cellular genotoxic stress response.
Yalkinoglu
A O
AO
Institut für Virusforschung, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany.
Heilbronn
R
R
Bürkle
A
A
Schlehofer
J R
JR
zur Hausen
H
H
D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D004279:DNA, Viral / Q000187:drug effects / Q000235:genetics*; D000229:Dependovirus / Q000187:drug effects / Q000235:genetics*; D005784:Gene Amplification; D005814:Genes, Viral; D006801:Humans; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology*; D010957:Plasmids; D013539:Simian virus 40 / Q000235:genetics
D004279:DNA, Viral; D008769:Methylnitronitrosoguanidine