Abstract
Stimulation of hepatic DNA synthesis can be achieved in the intact rat by α-hexachlorocyclohexane (α-HCH = α-benzene hexachloride). The extent of stimulation is high in the morning and low in the evening. These rhythmic variations in the rate of DNA synthesis are synchronized indirectly by the lightdark rhythm, but directly by the animal's feeding habits: Rats eat preferentially during the night. If the diurnal rhythm of food intake is abolished, the rhythmic fluctuations in the rate of DNA synthesis are no longer detectable; if rats are adapted to daily feeding periods of only 5 h, these fluctuations are pronounced and almost synchronized. Further experiments show that the time of feeding determines the time of DNA replication. It is concluded that food intake provides a „2nd stimulus” or permissive factor, which is required for the induction of DNA synthesis in a certain critical stage of the prereplicative phase. Labelling experiments with orotic acid suggest that food intake initially induces an increase of RNA synthesis.
The results indicate that controlled feeding schedules provide the possibility to synchronize, in the living animal, a proliferating population of hepatocytes. A hypothesis is derived which offers an explanation for the generation of the diurnal rhythm of cell proliferation in the liver.
Zusammenfassung
α-Hexachlorcyclohexan (α-HCH) stimuliert die DNS-Synthese in der Leber der Ratte. Das Ausmaß der Stimulierung ist hoch am Morgen und niedrig am Abend. Der wesentliche Zeitgeber für diese rhythmischen Variationen in der DNS-Synthese-Rate ist indirekt der Heil-Dunkel-Rhythmus, aber direkt die Freßgewohnheit der Ratten, die hauptsächlich nachts fressen. Wenn die Variationen in der Nahrungsaufnahme eliminiert werden, sind die rhythmischen Schwankungen der DNS-Synthese nicht mehr meßbar; wenn die Tiere täglich nur 5 Std gefüttert werden, treten sie verstärkt und weitgehend synchron auf. Weitere Experimente lassen erkennen, daß der Zeitpunkt der DNS-Replikation vom Zeitpunkt der Futteraufnahme bestimmt wird, die als „2. Stimulus” oder „permissive factor” in einem bestimmten Stadium der präreplikativen Phase fungiert. Markierungsversuche mit Orotsäure sprechen dafür, daß die Futterzufuhr zunächst einen Anstieg der RNS-Synthese-Rate auslöst.
Die Ergebnisse zeigen, daß die Anwendung des beschriebenen Fütterungs-Schemas die Synchronisation proliferierender Hepatozyten im lebenden Tier ermöglicht; es wird eine Hypothese formuliert, die die Entstehung der rhythmischen Schwankungen in der Zellproliferationsrate in der Leber erklären kann.
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Schulte-Hermann, R. Fütterungs-Rhythmen und die circadianen Variationen der Zellproliferation bei pharmakologisch induziertem Leberwachstum. Arch. Toxicol. 36, 235–245 (1976). https://doi.org/10.1007/BF00340531
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DOI: https://doi.org/10.1007/BF00340531