Modulation of carcinogen-induced polyoma DNA replication by organoselenium and organosulfur chemopreventive agents

Both chemical and physical carcinogens are potent inducers of asynchronous replication of various DNA tumor viruses. Employing H3 cells that carry an integrated copy of polyoma virus we have evaluated potential effects of known chemopreventive agents on carcinogen-induced polyoma DNA replication. The ability of well established organoselenium and organosulfur chemopreventive agents, in laboratory animals, to modulate polyoma DNA replication induced by AMMN or NNKOAc which are direct acting carcinogens derived from the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was examined. We demonstrate that both benzyl selenocyanate (BSC) and benzyl isothiocyanate (BITC) are capable of reducing the level of polyoma DNA replication induced by NNK-model compounds. BITC also reduced the transcriptional activity of polyoma sequences as measured through chloramphenicol-acetyl-transferase (CAT) assays using the polyoma regulatory region cloned upstream of the CAT gene. These results suggest that the mechanisms by which BSC and BITC exert their protective effects involve changes in the expression of cellular proteins which regulate transcription and replication of polyoma DNA sequences.