COMPARISON OF TRANSFORMATION BY MANGANESE SULFATE AND 5-AZACYTIDINE IN RAT-6 CELLS OVEREXPRESSING THE C-MYC ONCOGENE

Rat 6 cells are not transformed by treatment with the well-known carci nogens benzo[a]pyrene (BP) or N-methyl-N-nitro-N'-nitrosoguanidine (MN NG), Upon retroviral transduction of the mouse c-myc gene, Rat 6 cells showed mildly altered morphology and formed microcolonies in soft aga r; furthermore, they could be transformed by BP and MNNG to form large colonies in agar (Hsiao et al, (1992) Mel. Carcinogenesis, 5, 140-154 ), In the current report, we tested the sensitivity of the c-myc-overe xpressing cells (Rat 6/c-myc) to two additional chemicals: 5-azacytidi ne and MnSO4. These chemicals differ from the direct-acting mutagens t ested previously, 5-Azacytidine, a potent DNA methylation inhibitor, i nduced growth of large colonies in soft agar cultures of Rat 6 or Rat 6/c-myc cells, On the other hand, MnSO4 only induced transformation in Rat 6/c-myc cells, but not the parental Rat 6 cells, Transformants in duced by 5-azacytidine lost c-myc-induced apoptotic cell death, wherea s MnSO4-induced transformants showed a higher degree of apoptosis than the parental Rat 6/c-myc cells, These results suggest that MnSO4 co-o perates with overexpressed c-myc in inducing transformation, while 5-a zacytidine transformation is independent of c-myc overexpression and m ay involve alterations in the regulation of apoptosis.