Decreased DNA ploidy may constitute a mechanism of the reduced malignant behavior of B16 melanoma in aged mice

Orit Itzhaki, Ehud Skutelsky, Tatiana Kaptzan, Annette Siegal, Judith Sinai, Ginnette Schiby, Moshe Michowitz, Monica Huszar, Judith Leibovici*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Numerous data demonstrate a lower aggressiveness of tumors in aged as compared to young patients. The mechanisms underlying this phenomenon have not yet been completely elucidated. Several mechanisms have been shown, such as reduced tumor cell proliferation, increased apoptosis, immune response modifications and reduced angiogenesis in aged organism tumors. In the present study we report an incidentally found, not yet described mechanism, of the age-related reduced tumor progression, namely a decreased ploidy in B16 melanoma growing in old (near diploidy) as compared to young mice (tetraploidy). We surprisingly observed that tumor cells from aged mice were of smaller cell and nuclear size than those of young animals. Flow cytometry forward scatter data also showed a smaller cell size of melanoma cells from old mice. DNA flow cytometry profile comparison demonstrated that while B16 melanoma cells from young animals contained a high percentage of tetraploid cells, those derived from old animals were mostly close to diploid. A high importance has recently been attributed to aneuploidy as being at the origin of the genetic instability of neoplasia. Our results may support this notion. The transit from tetraploidy to near euploidy in melanoma cells growing in aged mice might avoid the genetic instability inherent to tumor progression.

Original languageEnglish
Pages (from-to)164-175
Number of pages12
JournalExperimental Gerontology
Issue number3
StatePublished - Mar 2008


  • Age-related malignancy
  • Aging microenvironment
  • B16 melanoma
  • DNA ploidy
  • Euploidization
  • Tetraploidy


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