Simian Virus 40 -- Chinese Hamster Kidney Cell Interaction. III. Characteristics of Chemical Induction in a Clone of Virogenic Transformed Cells

Abstract

A number of chemical and physical agents were screened to determine their effectiveness in inducing SV-40 production in a virogenic clone of SV-40-transformed Chinese hamster cells. Mitomycin C (MC) was the most effective inducing agent, and MC induction was further characterized. Levels of infectious SV-40 DNA were increased above control levels as early as 6 h after addition of MC to the culture medium and reached maximum levels by 48 h. Virus capsid (V) antigen and virions followed with a lag of about 24 h. V antigen production was sensitive to hydroxyurea, suggesting a dependence on virus DNA synthesis. The proportion of virus-producing cells (infectious centers) and the virus burst per cell were both stimulated by MC. Studies of 3H-thymidine incorporation demonstrated that the rate of SV-40 DNA synthesis was maximal at 48 h post-induction, at which time cellular DNA synthesis was almost abolished. Caffeine, at doses not toxic to non-induced cells, strongly inhibited SV-40 production in noninduced and induced cells, suggesting some role for DNA repair mechanisms.