Effect of Moloney murine leukemia virus on the carcinogenicity of 3-methylcholanthrene in normal rat kidney cells.

Normal rat kidney (NRK) cell were found to be resistant to neoplastic transformation by diverse carcinogenic chemicals. To study chemical-retroviral co-carcinogenesis in this cells they were infected with a low multiplicity of Moloney murine leukemia virus (M-MLV). Using a single cell cloning procedure, a virus-producing clone was isolated from the infected cells, which was shown to carry only one integrated M-MLV provirus per cell. It was found that this single provirus was sufficient to render the clone susceptible to transformation by 3-methylcholanthrene (3-MC). However this clone responded differently to the carcinogen at different passages after infection. When exposed to 3-MC at a low passage postinfection (passage 5), cell transformation was evident only after 11 subsequent subcultures. On the other hand when it was chemically treated at a high passage postinfection (passage 29), cell transformation could clearly be detected already at the next subculture after the chemical treatment. It is suggested that an M-MLV-mediated cumulative effect is necessary to complement the action of the carcinogen in order to complete the carcinogenic process in these cells. This cumulative viral effect appeared to be associated with a change in the control of the virus expression, since 3-MC was found to stimulate virus replication in this clone also only at the high passage postinfection. Indeed virus release by cells of isolated transformed foci, produced by the chemical-M-MLV co-carcinogenesis, was extremely higher than by untransformed cells.