Journal Article

Comparison of transformation by manganese sulfate and 5-azacytidine in Rat 6 cells overexpressing the <i>c-myc</i> oncogene

W.L.Wendy Hsiao, Grace Mendosa, Nayantara H. Kothari and Hung Fan

in Carcinogenesis

Volume 17, issue 12, pages 2771-2777
Published in print December 1996 | ISSN: 0143-3334
Published online December 1996 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.12.2771
Comparison of transformation by manganese sulfate and 5-azacytidine
                    in Rat 6 cells overexpressing the c-myc
                    oncogene

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Rat 6 cells are not transformed by treatment with the wellknown carcinogens benzo(a)pyrene (BP) or N-methyl-N-nitro-N' nitrosoguanidine (MNNG). Upon retroviral transduction of the mouse c-myc gene, Rat 6 cells showed mildly altered morphology and formed microcolonies in soft agar; furthermore, they could be transformed by BP and MNNG to form large colonies in agar (Hsiao et al. (1992) Mol. Carcinogenesis, 5, 140-154). In the current report, We tested the sensitivity of the c-myc-overexpressing cells (Rat 6/c-myc) to two additional chemicals: 5-azacytidine and MnSO4. These chemicals differ from the direct-acting mutagens tested previously. 5-Azacytidine, a potent DNA methylation inhibitor, induced 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 induced by 5-azacytidine lost c-myc-induced apoptotic cell death, whereas degree MnSO4 induced transformants showed a higher degree of apoptosis than the parental Rat 6/c-myc cells.These results suggest that MnSO4 co-operates with over-expressed c-myc in including transformation, while 5-azacytidine transformetion and may involve alterations in the regulation of apoptosis.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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