Early changes in growth control of cells in culture induced by a chemical carcinogen

The effects of the chemical carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on 'early events' in cellular response to growth stimulation were studied in quiescent (confluent and serum-starved) baby hamster kidney C13 and secondary mouse embryo cell cultures. After a short (one hour) exposure to MNNG (0.015 micrograms/ml), we observed an increase (up to 31%) in basal uridine uptake rates and a significant decrease in the stimulatory effect of serum on the uridine uptake capacity of the quiescent cells. These effects of MNNG are reminiscent of the permanent changes in growth regulation-related properties which accompany cell transformation. The results of this study suggest that MNNG interacts with a cellular target(s) which controls the rate of uridine uptake and other growth-related responses to serum factors. The effects of MNNG on cell responsiveness to growth regulators do not require active DNA synthesis and are observed long before transformation is evident, suggesting that non-DNA targets may be involved in the process of initiation of chemical carcinogenesis.