Smaaland R, Lote K, Sothern R B, Laerum O D
Gade Institute, Department of Pathology, Haukeland Hospital, University of Bergen, Norway.
Cancer Res. 1993 Jul 1;53(13):3129-38.
Significant circadian cell cycle variations with a maximal number of cells in S-phase during the night have been found in a series of 24 patients (18 men and 6 women) with histologically established non-Hodgkin's lymphomas. Pathological lymph nodes of a total of 26 patients were punctured and aspirated by fine needle technique every 4 h during a single 24-h time span. Twenty-four patients (92.3%) had Stage III or IV disease. Twelve patients (46.1%) had low grade, 10 patients (38.5%) had intermediate grade, and 4 patients (15.4%) had high grade lymphomas according to the Working Formulation. The samples were analyzed by flow cytometry, and DNA synthesis (S-phase) and ploidy were determined according to circadian stage. The individual mean 24-h S-phase varied from 2.2 +/- 1.2% (mean +/- SD) to 24.0 +/- 3.3%. Within the group of patients with low grade lymphomas, a wide range in mean S-phase from 2.4 +/- 1.2% to 9.2 +/- 2.8% was observed. The percentage variation within each patient between the lowest and highest S-phase as compared to the lowest value (range of change) during the 24-h time span varied from 21 to 353%, with a mean range of change of 128 +/- 19%. When each individual S-phase series was converted to percent of mean and combined for analysis by one-way analysis of variance to test for time-effect across 2 12-h time spans (8 p.m.-8 a.m. versus 8 a.m.-8 p.m.), S-phase variation according to circadian stage was found to be statistically significant (P < 0.004), with higher values found in the 8 p.m.-8 a.m. time span. By single cosinor analysis, S-phase yielded a near significant P value of 0.069 for the least-squares fit of a 24-h cosine to all data as percent of mean, with the acrophase found to be near midnight (0.05 h). For those patients with low and intermediate grade lymphomas and with mean S-phase values < 10.0%, we found that mean S-phase was higher during winter (5.8 +/- 0.4%) than during spring (3.8 +/- 0.3%) or during fall (3.6 +/- 0.3%) (P < 0.001, analysis of variance). Twenty-one of the 26 patients (80.8%) had an aneuploid, hypodiploid, or near diploid population in one or several of the repeated samples. For the whole series, the DNA indices for the aneuploid populations varied from 1.09 to 1.96, the median DNA index being 1.20.(ABSTRACT TRUNCATED AT 400 WORDS)
在一组24例经组织学确诊的非霍奇金淋巴瘤患者（18例男性和6例女性）中，发现了显著的昼夜细胞周期变化，夜间S期细胞数量最多。在单个24小时时间段内，每隔4小时用细针技术对总共26例患者的病理淋巴结进行穿刺和抽吸。24例患者（92.3%）处于III期或IV期疾病。根据工作分类法，12例患者（46.1%）为低级别淋巴瘤，10例患者（38.5%）为中级别淋巴瘤，4例患者（15.4%）为高级别淋巴瘤。通过流式细胞术分析样本，并根据昼夜阶段确定DNA合成（S期）和倍性。个体平均24小时S期从2.2±1.2%（平均值±标准差）到24.0±3.3%不等。在低级别淋巴瘤患者组中，观察到平均S期范围较宽，从2.4±1.2%到9.2±2.8%。与24小时时间段内最低值相比，每位患者最低和最高S期之间的百分比变化（变化范围）从21%到353%不等，平均变化范围为128±19%。当将每个个体的S期系列转换为平均值的百分比，并通过单因素方差分析进行合并分析，以测试两个12小时时间段（晚上8点至早上8点与早上8点至晚上8点）之间的时间效应时，发现根据昼夜阶段的S期变化具有统计学意义（P<0.004），晚上8点至早上8点时间段的值更高。通过单余弦分析，S期对所有数据作为平均值百分比的24小时余弦最小二乘拟合产生的P值接近显著水平0.069，峰相位接近午夜（0.05小时）。对于那些低级别和中级别淋巴瘤且平均S期值<10.0%的患者，我们发现冬季的平均S期（5.8±0.4%）高于春季（3.8±0.3%）或秋季（3.6±0.3%）（方差分析，P<0.001）。26例患者中的21例（80.8%）在一个或多个重复样本中有非整倍体、亚二倍体或近二倍体群体。对于整个系列，非整倍体群体的DNA指数从1.09到1.96不等，DNA指数中位数为1.20。（摘要截断于400字）
