Growth and fatty acid metabolism of human breast cancer (MCF-7) xenografts in nude rats: impact of constant light-induced nocturnal melatonin suppression.
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.
Blask
David E
DE
Laboratory of Chrono-Neuroendocrine Oncology, Bassett Research Institute, Cooperstown, NY 13326, USA. david.blask@bassett.org
Dauchy
Robert T
RT
Sauer
Leonard A
LA
Krause
Jean A
JA
Brainard
George C
GC
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D000991:Antithrombins / Q000378:metabolism / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D002940:Circadian Rhythm; D005260:Female; D006801:Humans; D008027:Light / Q000009:adverse effects*; D019787:Linoleic Acid / Q000378:metabolism*; D008041:Linoleic Acids / Q000378:metabolism / Q000493:pharmacokinetics; D008550:Melatonin / Q000096:biosynthesis* / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D010870:Pineal Gland / Q000502:physiology; D014183:Transplantation, Heterologous
D000975:Antioxidants; D000991:Antithrombins; D008041:Linoleic Acids; C024348:13-hydroxy-9,11-octadecadienoic acid; D019787:Linoleic Acid; D008550:Melatonin