Growth and fatty acid metabolism of human breast cancer (MCF-7) xenografts in nude rats: impact of constant light-induced nocturnal melatonin suppression

Breast Cancer Res Treat. 2003 Jun;79(3):313-20. doi: 10.1023/a:1024030518065.

Abstract

The nocturnal melatonin (MLT) surge is a relevant oncostatic signal for a variety of experimental malignancies. Population studies support the hypothesis that exposure to light at night may represent a new risk factor for breast cancer possibly through the suppression of pineal MLT production and/or circadian disruption. We tested the ability of constant light exposure to suppress MLT production in female nude rats and stimulate the growth of tissue-isolated MCF-7 human breast cancer xenografts via increased tumor linoleic acid (LA) metabolism. Rats maintained on an alternating light/dark cycle (L:D group) exhibited a robust circadian MLT rhythm that was abolished following constant light exposure. During the exposure of animals bearing tissue-isolated human MCF-7 breast cancer xenografts to constant light, the rate of tumor growth markedly increased relative to the L:D group. Tumor LA uptake and its metabolism to the mitogen 13-hydroxyoctadecadienoic acid (13-HODE) were also substantially higher under constant light conditions. This is the first biological evidence for a potential link between constant light exposure and increased human breast oncogenesis involving MLT suppression and stimulation of tumor LA metabolism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Antithrombins / metabolism
  • Antithrombins / pharmacokinetics
  • Breast Neoplasms / pathology*
  • Cell Transformation, Neoplastic
  • Circadian Rhythm*
  • Female
  • Humans
  • Light / adverse effects*
  • Linoleic Acid / metabolism*
  • Linoleic Acids / metabolism
  • Linoleic Acids / pharmacokinetics
  • Melatonin / biosynthesis*
  • Melatonin / pharmacology*
  • Mice
  • Mice, Nude
  • Pineal Gland / physiology
  • Transplantation, Heterologous

Substances

  • Antioxidants
  • Antithrombins
  • Linoleic Acids
  • 13-hydroxy-9,11-octadecadienoic acid
  • Linoleic Acid
  • Melatonin