Bartsch C, Bartsch H, Buchberger A, Rokos H, Mecke D, Lippert T H
Section of Clinical Pharmacology, University Women's Hospital, Tübingen, Germany.
Oncology. 1995 Jul-Aug;52(4):278-83. doi: 10.1159/000227473.
Nocturnal (23.00-07.00 h) urinary melatonin and total biopterin (tBI; after acidic oxidation of reduced biopterins) were analyzed during the growth of two passages of a mammary tumor line in female F344 Fischer rats. In addition, nocturnal (02.00-03.00 h) peak concentrations of pineal melatonin in plasma were analyzed when tumors had reached comparable average tumor volumes of 25-30 cm3. Since tetrahydrobiopterin (BH4) is produced by murine macrophages in response to interferon-gamma released by activated T lymphocytes, measurements of tBI can serve to estimate the state of cellular immunity. At passage 2, a slow-growing localized carcinosarcoma, tBI showed a progressing increase during tumor growth reaching more than 200% (p < 0.05-0.005) of controls by the end of the experiment. Urinary and plasma melatonin were elevated by 30-50% (p < 0.05) and 42% respectively. At passage 12, a fast-growing metastasizing sarcoma, a depression of about 20-30% was found for tBI (p < 0.05) and urinary melatonin (p < 0.025); plasma melatonin was depleted by 70% (p < 0.005). Parallel changes of both parameters at each tumor passage indicate a close link between the pineal hormone melatonin and cellular immunity. The opposite trends observed at the two passages indicate a clear stimulation of the immune system and the pineal gland at early but inhibition at advanced stages of cancer.
在雌性F344 Fischer大鼠乳腺肿瘤细胞系传代培养的两个阶段，分析了夜间（23:00 - 07:00）尿中褪黑素和总生物蝶呤（tBI；还原型生物蝶呤经酸性氧化后）。此外，当肿瘤平均体积达到25 - 30 cm³时，分析了血浆中松果体褪黑素的夜间（02:00 - 03:00）峰值浓度。由于四氢生物蝶呤（BH4）由小鼠巨噬细胞在活化T淋巴细胞释放的γ干扰素作用下产生，tBI的测量可用于评估细胞免疫状态。在传代2时，是一种生长缓慢的局部癌肉瘤，tBI在肿瘤生长过程中持续增加，到实验结束时达到对照组的200%以上（p < 0.05 - 0.005）。尿中和血浆中的褪黑素分别升高了30 - 50%（p < 0.05）和42%。在传代12时，是一种生长迅速的转移性肉瘤，发现tBI（p < 0.05）和尿褪黑素（p < 0.025）降低了约20 - 30%；血浆褪黑素减少了70%（p < 0.005）。每个肿瘤传代阶段这两个参数的平行变化表明松果体激素褪黑素与细胞免疫之间存在密切联系。在两个传代阶段观察到的相反趋势表明，癌症早期免疫系统和松果体受到明显刺激，而晚期则受到抑制。
