Circadian variation in O6‐alkylguanine‐DNA alkyltransferase activity in circulating blood mononuclear cells of healthy human subjects
Circadian variation in O6‐alkylguanine‐DNA alkyltransferase activity in circulating blood mononuclear cells of healthy human subjects
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健康人类受试者循环血液单核细胞中 O6-烷基鸟嘌呤-DNA 烷基转移酶活性的昼夜变化
DOI：
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发表时间：
2001
影响因子：
6.4
通讯作者：
P. Chollet
中科院分区：
文献类型：
--
作者：
Cécile Marchenay;E. Cellarier;F. Lévi;C. Rolhion;F. Kwiatkowski;B. Claustrat;J. Madelmont;P. Chollet
细胞毒性剂如氯乙基亚硝基脲（CENUs）主要在O 6-鸟嘌呤位置上烷基化DNA。这种高度致突变的损伤可以通过O 6-烷基鸟嘌呤-DNA烷基转移酶（AGT）修复，该酶通过将烷基接受到其活性位点的半胱氨酸残基来去除烷基。AGT活性在小鼠肝脏中显示昼夜节律，与CENU耐受性一致。我们研究AGT活性是否显示在人类循环单核细胞（MNCs）的昼夜节律。该研究在12名19至31岁的健康志愿者中进行。昼夜节律同步验证休息/活动周期与腕关节活动和血浆皮质醇和褪黑激素的节奏进行评估。受试者住院24小时，并在08：00、12：00、16：00、20：00、22：00、00：00、02：00、04：00和08：00采集血样过夜。血液采样后立即在Ficoll上分离MNC，并在-196 °C下冷冻，直至通过HPLC测定AGT活性。平均AGT活性（± SEM）从中午（谷值）的821 ± 67 fmol/mg总蛋白变化至午夜（峰值）的1055 ± 80 fmol/mg，即，30%左右。通过方差分析（p < 0.009）和余弦分析（p < 0.02），对MNC中AGT活性（00：30 ± 210 min时的峰值相± SD）以及MNC循环计数和血浆皮质醇和褪黑素浓度进行了统计学验证。尽管AGT活性节律的程度存在个体差异（根据受试者或多或少明显），但AGT活性在我们的健康研究组受试者的人MNC中显示出昼夜节律。结果保证进一步研究AGT的节律性在循环的MNC和癌症患者的靶组织，作为一个先决条件的临床试验的时间治疗与烷化剂。Int. J. Cancer 91：60-66，2001.© 2001 Wiley利斯公司
Cytotoxic agents such as chloroethylnitrosoureas (CENUs) mostly alkylate DNA on the O6‐guanine position. This highly mutagenic lesion can be repaired by O6‐alkylguanine‐DNA alkyltransferase (AGT), which removes the alkyl group by accepting it to the cysteine residue of its active site. AGT activity displayed a circadian rhythm in mouse liver, coincident with that of CENU tolerability. We investigated whether AGT activity displayed a circadian rhythm in human circulating mononuclear cells (MNCs). The study was performed in 12 healthy volunteers aged 19 to 31 years. Circadian synchronization was verified with rest/activity cycle as assessed with wrist actigraphy and plasma cortisol and melatonin rhythms. Subjects were hospitalized for 24 hr and blood samples were obtained at 08:00, 12:00, 16:00, 20:00, 22:00, 00:00, 02:00, 04:00 and 08:00 overnight. MNCs were isolated on Ficoll immediately after blood sampling and frozen at −196°C until AGT activity determination by HPLC. Mean AGT activity (± SEM) varied from 821 ± 67 fmol/mg of total proteins at noon (trough), up to 1055 ± 80 fmol/mg at midnight (peak), i.e., by ∼30%. A circadian rhythm was statistically validated with both analysis of variance (p < 0.009) and cosinor (p < 0.02) for AGT activity in MNCs (acrophase ± SD at 00:30 ± 210 min) as well as for MNC circulating count and for plasma cortisol and melatonin concentrations. Despite individual variations in the extent of AGT activity rhythm (more or less pronounced according to subject), AGT activity displayed a circadian rhythm in human MNCs of our healthy study group subjects. The results warrant to further investigate AGT rhythmicity both in circulating MNCs and in target tissues of cancer patients, as a prerequisite for clinical testing of chronotherapy with alkylating agents. Int. J. Cancer 91:60–66, 2001. © 2001 Wiley‐Liss, Inc.
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DOI：
10.1016/0921-8734(89)90028-3
发表时间：
1989
期刊：
Mutation research
影响因子：
--
作者：
Edwards,JA;Wang,LG;Setlow,RB;Kaminskas,E
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Kaminskas,E
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DOI：
--
发表时间：
2000
期刊：
Cancer research.
影响因子：
--
作者：
Srivenugopal,KS;Mullapudi,SR;Shou,J;Hazra,TK;Ali-Osman,F
通讯作者：
Ali-Osman,F
影响因子：
11.2
作者：
F. Ali-Osman
通讯作者：
F. Ali-Osman
正常结肠组织和结肠癌中的 O6-烷基鸟嘌呤-DNA 烷基转移酶。
影响因子：
3.1
作者：
White,A;Kibitel,J;Garcia,Y;Belanich,M;Yarosh,D;Wideroff,J;Levin,L;Held,D;Fuchs,A;Citron,M
通讯作者：
Citron,M
影响因子：
11.2
作者：
Istvan Boldogh;C. Ramana;C. Ramana;Zhenping Chen;Tapan Biswas;T. Hazra;Sabine Grösch;T. Grombacher;Sankar Mitra;Bernd Kaina
通讯作者：
Istvan Boldogh;C. Ramana;C. Ramana;Zhenping Chen;Tapan Biswas;T. Hazra;Sabine Grösch;T. Grombacher;Sankar Mitra;Bernd Kaina