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Fish oil slows S phase progression and may cause upstream shift of DHFR replication origin ori-beta in CHO cells

Nawfal W Istfan1, Zhi-Yi Chen, Sybille Rex

  • 1Section of Endocrinology, Diabetes, and Nutrition, Department of Medicine, Boston University School of Medicine, 88 E Newton Street, Evans 201, Boston, MA 02118, USA. nsteph3@cs.com

American Journal of Physiology. Cell Physiology
|September 13, 2002
PubMed

Insights

Fish oils (FOs) slow cell cycle progression in mammalian cells by altering DNA replication initiation. This suggests novel mechanisms by which dietary fats impact cell proliferation and DNA synthesis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Fish oils (FOs) contain n-3 polyunsaturated fatty acids linked to reduced tumor cell growth.
  • The precise mechanisms by which FOs affect cellular processes remain under investigation.

Purpose of the Study:

  • To investigate the impact of fish oil on cell cycle kinetics and DNA replication in Chinese hamster ovary cells.
  • To explore potential alterations in DNA replication origin usage induced by fish oil treatment.

Main Methods:

  • Cells were treated with fish oil or corn oil and analyzed using 5-bromo-2'-deoxyuridine (BrdU) labeling and flow cytometry.
  • The nascent strand length assay and PCR were employed to map replication origins, specifically ori-beta near the dihydrofolate reductase gene.

Main Results:

  • Fish oil treatment resulted in slower progression through S phase and prolonged S phase duration.
  • DNA replication initiation in fish oil-treated cells occurred at a novel site upstream of the characterized ori-beta, indicating a shift in replication origin usage.

Conclusions:

  • Fish oil consumption alters mammalian cell cycle kinetics, specifically by affecting DNA replication timing and origin selection.
  • These findings suggest a novel mechanism involving spatial-temporal organization of replication origins through which dietary fats influence cell proliferation.

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