ABSTRACT
An animal system is described that allows the analysis of the interaction of persisting hamster papovavirus (HaPV) genomes with the tumor-promoting phorbol ester TPA. In a colony of HaPV-bearing Syrian golden hamsters, extrachromosomal HaPV genomes were detected by Southern blot hybridization in DNA isolated from skin biopsies. Chronic topical treatment of hamsters with TPA resulted in a dramatic increase of viral DNA in skin cells at the site of TPA application. After finishing the TPA treatment, the amount of extrachromosomal viral DNA declined but was still enhanced more than three months thereafter. This model offers the possibility of investigating, at the molecular level, the initiating role of virus in tumorigenesis.
Subject(s)
Carcinogens/pharmacology , Cocarcinogenesis , DNA Tumor Viruses/drug effects , Papillomaviridae/drug effects , Polyomaviridae , 9,10-Dimethyl-1,2-benzanthracene/pharmacology , Animals , Carcinoma/chemically induced , Cricetinae , DNA Tumor Viruses/genetics , DNA, Viral/analysis , Drug Interactions , Male , Mesocricetus , Papilloma/chemically induced , Papillomaviridae/genetics , Skin Neoplasms/chemically induced , Tetradecanoylphorbol Acetate/pharmacologyABSTRACT
The antiviral effects of four compounds, phosphonoacetate, phosphonoformate, acycloguanosine, and purified human lymphoblastic interferon, were tested against two neurotropic herpesviruses, herpesvirus platyrrhine and herpes simplex virus, and two oncogenic herpesviruses, herpesvirus saimiri and herpesvirus ateles. All four compounds induced different degrees of inhibition of these herpesviruses. Phosphonoacetate and phosphonoformate at concentrations of 50 micrograms/ml or greater showed powerful antiviral activities. Interferon was more effective against herpesvirus saimiri and herpesvirus ateles, the two oncogenic viruses. Herpes simplex virus and the oncogenic herpesviruses were effectively inhibited by acycloguanosine, whereas herpesvirus platyrrhine proved to be resistant. The simian herpesviruses required a higher concentration of phosphonoformate, phosphonoacetate, and acycloguanosine for antiviral action. The antiviral action of all four compounds was contingent on the continued presence of the compounds in the infected cell culture medium.
