The essential role of Rauscher leukemia virus (RLV) multiplication in viral-chemical co-carcinogenesis was investigated by the use of ethidium bromide (EtBr) as an inhibitor of viral complementary DNA (cDNA) integration in the host genome. EtBr inhibited co-carcinogenic transformation when present at the time of RLV inoculation but was ineffective when added to preinfected cells. Inhibitors of protein synthesis, puromycin and cyclohexamide also inhibited co-carcinogenic transformation of chronically infected cells. Purified rat interferon used at a concentration which inhibited 85% of RLV production did not modify the course of co-carcinogenic transformation. The implications of these observations in terms of the possible role of the virus-specific protein (s) in the co-carcinogenic process are discussed.

No abstract

Thirteen chemicals, eight carcinogenic and five closely related noncarcinogenic analogues, were tested to establish the validity of a simultaneous procedure for the in vitro assay of potential carcinogens and mutagens. The assay utilizes Fischer rat embryo (FRE) cells infected with Rauscher leukemia virus and simultaneously measures the induction of cellular transformation (growth in soft agar) and mutagenesis (ouabain resistance) by chemicals. An activation procedure for the metabolic conversion of the procarcinogens and promutagens to biologically active forms is described. All chemicals that produced transformation in the FRE system also induced a significant increase in ouabain resistance. The significance and the potential uses of this assay are discussed.