Academic journal article Scandinavian Journal of Work, Environment & Health

Circadian Gene Expression in Peripheral Blood Leukocytes of Rotating Night Shift Nurses

Academic journal article Scandinavian Journal of Work, Environment & Health

Circadian Gene Expression in Peripheral Blood Leukocytes of Rotating Night Shift Nurses

Article excerpt

Objective It has been hypothesized that the underlying mechanism of elevated breast cancer risk among long-term, night-working women involves circadian genes expression alteration caused by exposure to light at night and/or irregular work hours. The aim of the present study was to determine the effect of rotating night shift work on expression of selected core circadian genes.

Methods The cross-sectional study was conducted on 184 matched nurses and midwives, who currently work either day or rotating night shifts, to determine the effect of irregular work at night on circadian gene expression in peripheral blood leukocytes. Transcript levels of BMAL1, CLOCK, CRY1, CRY2, PER1, PER2, and PER3 were determined by means of quantitative real-time polymerase chain reaction (PCR).

Results After adjusting for hour of blood collection, there were no statistically significant changes of investigated circadian genes among nurses and midwives currently working rotating night shifts compared to nurses working day shifts. The highest expression of PERI messenger ribonucleic acid (mRNA) was observed for women currently working shifts who had worked >15 years in rotating night shift work. PER1 gene expression was associated with the lifetime duration of rotating night shift work among women currently working night shifts (P=0.04). PER1 and PER3 transcript levels in blood leukocytes were significantly down-regulated in the later versus early hours of the morning between 06.00-10.00 hours (β-coefficient -0.226, P=0.001 and β-coefficient -0.181, P<0.0001, respectively).

Conclusions These results suggest that current rotating night shift work does not affect circadian gene expression in human circulating leukocytes. In analysis of the peripheral clock in human studies, the hour of blood collection should be precisely specified.

Key terms cancer; chronotype; night work; nurse; shift work; shift worker; sleep.

Circadian rhythm, observed in various metabolic and physiological processes, is governed by the endogenous clock found in the suprachiasmatic nucleus (SCN) of the hypothalamus and by peripheral clocks. The circadian system of the organism acts independently of external cues, but it can adapt to environmental conditions, such as light, temperature, meals/feeding etc. The circadian clock in the SCN is synchronized to external cues, and it coordinates the peripheral clock by sending signals to peripheral tissues (1). The molecular mechanism of the self-sustained circadian system of the organism involves circadian genes. Circadian genes presenting oscillatory transcriptional-translational feedback loops have been found not only in the SCN, but also in peripheral tissues, including human peripheral leukocytes. The biological clock is controlled by several genes, including BMALl, CLOCK, Period (PER) and Cryptochrome (CRY) (2).

Some epidemiological studies have found that longterm, night- working women have a higher risk of breast cancer than women who do not work at night (3). One of several proposed mechanisms underlying cancer risk among individuals exposed to light at night involves circadian genes expression alteration (4). Circadian genes may play an important role in the control of multiple biological processes (5), including DNA repair, oxidative stress, maintenance of genomic stability, cell proliferation, and apoptosis (6, 7). Therefore, they may have important relevance to the carcinogenic process. Alteration of circadian genes was found to be associated with various disorders in humans, including sleep and mental disorders, cardiovascular diseases, obesity, impaired glucose tolerance, alcohol abuse, and cancer (8-12).

It has been widely observed that a molecular feedback loop exists for specific clock genes that act as positive and as well negative regulators of the biological clock. Moreover, circadian genes expression among humans is reported to be similar to that observed in rodent peripheral tissue, although tissue-specific clock genes expression patterns were also observed (1). …

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