Abrahamsen J F, Smaaland R, Sandberg S, Aakvaag A, Lote K
Gade Institute, Department of Pathology, Haukeland Hospital, University of Bergen, Norway.
Eur J Haematol. 1993 Apr;50(4):206-12. doi: 10.1111/j.1600-0609.1993.tb01922.x.
Serum cortisol, circulating white blood cells and DNA cell cycle distribution in bone marrow cells were measured during daytime (11.00) and at midnight (24.00) over single 24-hour periods in 15 cancer patients. The neutrophils and fraction of bone marrow cells in S-phase showed the same circadian variation as cortisol with higher values in daytime as compared to midnight in 11 patients with a normal cortisol rhythm (p < 0.05). The lymphocytes, eosinophils and basophils all had significantly higher values at midnight as compared to daytime. There were significant correlations between cortisol and neutrophils, lymphocytes, eosinophils and basophils. The correlation between neutrophils and fractions of bone marrow cells in S-phase and S + G2/M-phase were highly significant (r = 0.74, p = 0.0001 and r = 0.72, p = 0.0001, respectively). In 8 of 13 patients (61.5%) without bone marrow infiltration both cortisol and neutrophils showed identical circadian variation as bone marrow cells in S-phase and S + G2/M-phase. Furthermore, for the total series a significant correlation between S-phase, cortisol and neutrophils was found by multiple regression analysis (p < 0.0001). These findings strengthen the possibility of using the circadian variation in cortisol and neutrophils as marker rhythms for circadian variation in bone marrow proliferation, thus allowing optimization of cytotoxic therapy and individualization of chronotherapy.
在15例癌症患者的单个24小时时间段内，于白天（11:00）和午夜（24:00）测量血清皮质醇、循环白细胞以及骨髓细胞中的DNA细胞周期分布。在11例皮质醇节律正常的患者中，中性粒细胞以及处于S期的骨髓细胞比例与皮质醇呈现相同的昼夜节律变化，白天的值高于午夜（p < 0.05）。淋巴细胞、嗜酸性粒细胞和嗜碱性粒细胞在午夜时的值均显著高于白天。皮质醇与中性粒细胞、淋巴细胞、嗜酸性粒细胞和嗜碱性粒细胞之间存在显著相关性。中性粒细胞与处于S期以及S + G2/M期的骨髓细胞比例之间的相关性高度显著（分别为r = 0.74，p = 0.0001和r = 0.72，p = 0.0001）。在13例无骨髓浸润的患者中，有8例（61.5%）的皮质醇和中性粒细胞与处于S期以及S + G2/M期的骨髓细胞呈现相同的昼夜节律变化。此外，对于整个系列，通过多元回归分析发现S期、皮质醇和中性粒细胞之间存在显著相关性（p < 0.0001）。这些发现增强了将皮质醇和中性粒细胞的昼夜节律变化用作骨髓增殖昼夜节律变化的标记节律的可能性，从而有助于优化细胞毒性疗法并实现时辰疗法的个体化。
