CIRCADIAN-RHYTHM OF CELLULAR PROLIFERATION IN THE HUMAN RECTAL MUCOSA

CIRCADIAN-RHYTHM OF CELLULAR PROLIFERATION IN THE HUMAN RECTAL MUCOSA
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DOI:
10.1016/0016-5085(91)90019-h
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发表时间:
1991-08-01
期刊:
影响因子:
29.4
通讯作者:
RUBIN, NH
RUBIN, NH
中科院分区:
医学1区
文献类型:
--
作者:
BUCHI, KN;MOORE, JG;RUBIN, NH

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胃肠道粘膜DNA合成和细胞增殖的昼夜节律已经在动物模型中得到了很好的记录。这项研究旨在确定在人类直肠上皮中是否也存在类似的节律:对16名健康男性进行了24项研究,分别在禁食(n=14)和进食(n=10)的条件下进行。直肠黏膜活检标本每隔2~3小时经直肠镜检查一次,持续24小时。对粘膜标本进行了氚胸苷掺入DNA的体外测量。喂食和一天中的时间都对直肠粘膜细胞DNA中胸腺嘧啶核苷的掺入速率有影响。禁食和进食受试者的胸腺嘧啶核苷掺入均显示出明显的昼夜节律,在上午7点左右达到高峰。禁食可在不改变节律的情况下降低总体平均胸腺嘧啶核苷摄取。胸腺嘧啶核苷的摄取通常反映了样本组织中DNA合成量。因此,这些数据可能对使用在DNA合成过程中特定活性的药物的癌症化疗方案的设计很重要。
Circadian rhythms of DNA synthesis and cellular proliferation in the gastrointestinal mucosa have been well documented in animal models. This investigation was designed to determine whether similar rhythms could be demonstrated in the human rectal epithelium: 24 studies were performed in 16 healthy men under fasting (n = 14) and fed (n = 10) conditions. Rectal mucosal biopsy specimens were obtained through a proctoscope every 2 or 3 hours for a 24-hour span. Ex vivo measurements of tritiated thymidine incorporation into DNA were made on the mucosal samples. Feeding and time of day were each found to have an effect on the rate of thymidine incorporation into the DNA of rectal mucosal cells. Both fasted and fed subjects showed significant circadian rhythms in thymidine incorporation, which peaked at about 7am. Fasting lowered the overall mean thymidine uptake without altering the rhythm. Thymidine uptake generally reflects the amount of DNA synthesis in the sampled tissue. Therefore, these data may be important in the design of cancer chemotherapeutic regimens that use drugs specifically active during DNA synthesis.