6DMAP inhibition of early cell cycle events and induction of mitotic abnormalities

Marcella Simili, Paola Pellerano, Simona Pigullo, Gaia Tavosanis, Laura Ottaggio, Louis De Saint-Georges, Stefania Bonatti

Research output: Contribution to journalArticlepeer-review


N-6 dimethylaminopurine (6DMAP) has been shown to induce aberrant mitosis in different cell types including Chinese hamster fibroblasts (CHEF/18). The mechanism of action and the cellular targets, however, are still not clear. We showed previously that in CHEF/18 cells this compound inhibits DNA synthesis with a kinetic of inhibition suggestive of an effect on early events of the cell cycle. In this paper we investigated which cellular targets were affected by 6DMAP and found that: (i) the compound inhibits phosphorylation of ribosomal protein S6 and activation of the 70 KDa S6 kinase (p70(S6k)) known to be activated by epidermal growth factor (EGF) in keeping with the notion that it is a protein kinase inhibitor; however the inhibition in vivo appears to be specific as MAP kinase phosphorylation is not inhibited; (ii) 6DMAP drastically affects cytoskeletal components leading to a rapid morphological change in most cells. These data, together with the findings that the dose range and the treatment time effective in inducing the micronuclei containing chromosomes were the same as for DNA synthesis inhibition, suggest that a disturbance in G1 of signal transduction pathways may contribute to abnormal mitosis.

Original languageEnglish
Pages (from-to)313-319
Number of pages7
Issue number5
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Toxicology
  • Health, Toxicology and Mutagenesis


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