d-609 and Cell-Transformation--Viral

Xanthate derivatives of primary alcohols with antiviral properties exert, in combination with monocarboxylic C11 or C12 acids a pronounced anti-tumor activity in vitro and in vivo. Tricyclodecan-9-yl-xanthogenate (D609) or cyclododecyl xanthogenate (D435) when administered together with either undecanoic or dodecanoic acid to various transformed animal and human tumor cells (displaying low serum requirement) cause cell death. In contrast, normal cells from which transformed derivatives arose, were unaffected.

Topics: Animals; Antineoplastic Agents; Antiviral Agents; Bridged-Ring Compounds; Carboxylic Acids; Cell Line; Cell Survival; Cell Transformation, Viral; Drug Synergism; Humans; Hydrogen-Ion Concentration; Lymphocytes; Norbornanes; Thiocarbamates; Thiones

Bovine papilloma virus-transformed hamster embryo fibroblasts (HEF-BPV) reacted to exposure to tricyclodecan-9-yl-xanthogenate (D609) with immediate reversion to the growth kinetics and the flat morphology of the untransformed parental cells. After six population doublings in the presence of D609, clones which displayed an untransformed morphology in the absence of D609 arose with a high frequency (90%). Such clones had reacquired a limited in vitro lifetime and had lost the ability to induce tumors in athymic nude mice. At the molecular level the revertant clones had lost all extrachromosomal monomeric BPV-1 DNA molecules. Only high molecular weight (HMW) oligomeric BPV-1 DNA that was probably integrated into the cellular genome was still detectable in a methylated transcriptionally inactive state. In contrast to transformed cells, the revertant clones no longer transcribed BPV-1-specific mRNA molecules, but were stimulated by a tumor promoter to transient viral gene expression. This article provides direct evidence for the complete reversibility of the property of "immortality".

Topics: Animals; Bovine papillomavirus 1; Bridged-Ring Compounds; Cell Transformation, Viral; Clone Cells; Cricetinae; DNA, Viral; Fibroblasts; Mesocricetus; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental; Norbornanes; Papillomaviridae; RNA, Neoplasm; RNA, Viral; Tetradecanoylphorbol Acetate; Thiocarbamates; Thiones; Transcription, Genetic