Cell Susceptibility to the Cytotoxic Effect of the Carcinogens Dimethylnitrosamine and N-Nitrosomethylurea

Summary

Transformed hamster cells showed a resistance to the cytotoxic effect of dimethylnitrosamine (DMNA), whereas normal hamster cells were either susceptible or resistant. Hamster cells were still susceptible to the cytotoxic effect of DMN A when tested 4 months after the increase in cellular lifespan induced by DMNA. However, at a later time in culture there was a selection of resistant cells which showed a growth advantage in vitro and in vivo. A related nitroso compound N-nitrosomethylurea (NMU) was cytotoxic to normal and even more cytotoxic to transformed hamster cells. This difference with NMU seems related to the difference in the growth rate of the normal and transformed cells. The results indicate that susceptibility and resistance with different types of cells are found with DMNA, a carcinogenic nitroso compound which has to be converted enzymatically to the cytotoxic intermediate, while no such differential cytotoxicity is found with NMU, which seems to be nonenzymatically converted to the cytotoxic intermediate. DMNA, in contrast to benzo[a]pyrene (BP), was cytotoxic to normal human cells and, like BP, was not cytotoxic to transformed human cells. This difference suggests that the enzyme involved in the conversion of DMNA to a cytotoxic derivative is not identical with BP hydroxylase.