Enhancement of replication of Epstein-Barr virus DNA in human lymphoblastoid cell lines by N-methyl-N'-nitro-N-nitrosoguanidine.

Abstract

N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) is a potent carcinogen that alkylates nucleic acids. Interaction of MNNG with human lymphoblastoid cell lines carrying Epstein-Barr virus (EBV) was studied. Treatment of virus-producing cells (P3HR-1) with MNNG resulted in an approximately 3-fold increase in EBV genome copies per cell as determined by cRNA--DNA hybridization. This effect was not observed in a non-virus-producer line (Raji). Dose-response studies indicated that the optimum concentration was between 0.5 micrograms and 2 micrograms/ml. This same dose range was most effective in inhibiting cell proliferation both of P3HR-1 and Raji cells. Concomitant treatment of P3HR-1 cells with MNNG and 12-O-tetradecanoylphorbol-13-acetate gave an additive increase to 9-fold of the number of EBV genome copies per cell. Pretreatment of Raji cells with MNNG followed by superinfection with P3HR-1 virus resulted in a 35% enhancement of EBV DNA replication as analyzed by density centrifugation. In contrast, Raji cells superinfected with MNNG-treated EBV showed a marked reduction in EBV DNA replication which indicates that the lesions produced in the viral genome by the drug interferred with the infectious potential of the virus.