title: Irradiation with X-rays phase-advances the molecular clockwork in liver, adrenal gland and pancreas.
abstract: The circadian clock of man and mammals shows a hierarchic organization. The master clock, located in the suprachiasmatic nuclei (SCN), controls peripheral oscillators distributed throughout the body. Rhythm generation depends on molecular clockworks based on transcriptional/translational interaction of clock genes. Numerous studies have shown that the clockwork in peripheral oscillators is capable to maintain circadian rhythms for several cycles in vitro, i.e. in the absence of signals from the SCN. The aim of the present study is to analyze the effects of irradiation with X-rays on the clockwork of liver, adrenal and pancreas. To this end organotypic slice cultures of liver (OLSC) and organotypic explant cultures of adrenal glands (OAEC) and pancreas (OPEC) were prepared from transgenic mPer2(luc) mice which express luciferase under the control of the promoter of an important clock gene, Per2, and allow to study the dynamics of the molecular clockwork by bioluminometry. The preparations were cultured in a membrane-based liquid-air interface culturing system and irradiated with X-rays at doses of 10 Gy and 50 Gy or left untreated. Bioluminometric real-time recordings show a stable oscillation of all OLSC, OAEC and OPEC for up to 12 days in vitro. Oscillations persist after irradiation with X-rays. However, a dose of 50 Gy caused a phase advance in the rhythm of the OLSC by 5 h, in the OPEC by 7 h and in the OAEC by 6 h. Our study shows that X-rays affect the molecular clockwork in liver, pancreas and adrenal leading to phase advances. Our results confirm and extend previous studies showing a phase-advancing effect of X-rays at the level of the whole animal and single cells.
authors.affiliation: Dr. Senckenbergisches Chronomedizinisches Institut , Frankfurt am Main , Germany .
authors.forename: Mareike Hildegard
authors.initials: MH
authors.lastname: Müller
authors.forename: Franz
authors.initials: F
authors.lastname: Rödel
authors.forename: Udo
authors.initials: U
authors.lastname: Rüb
authors.forename: Horst-Werner
authors.initials: HW
authors.lastname: Korf
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism / Q000528:radiation effects*; D000818:Animals; D057906:Circadian Clocks / Q000235:genetics / Q000528:radiation effects*; D005786:Gene Expression Regulation / Q000528:radiation effects; D017930:Genes, Reporter; D008099:Liver / Q000378:metabolism / Q000528:radiation effects*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010179:Pancreas / Q000378:metabolism / Q000528:radiation effects*; D056950:Period Circadian Proteins / Q000235:genetics*; D017440:Photoperiod; D011401:Promoter Regions, Genetic / Q000528:radiation effects; D011829:Radiation Dosage; D013997:Time Factors; D046509:Tissue Culture Techniques; D014965:X-Rays
chemical_list: C513312:Per2 protein, mouse; D056950:Period Circadian Proteins
keywords: Circadian rhythm; X-rays; clock gene bioluminescence; phase-shift; tissue culture