Long-time expression of DNA repair enzymes MGMT and APE in human peripheral blood mononuclear cells

被引:29
作者
Janssen, K
Eichhorn-Grombacher, U
Schlink, K
Nitzsche, S
Oesch, F
Kaina, B
机构
[1] Prof Dr G Grimmer Fdn, Biochem Inst Environm Carcinogens, D-22927 Grosshansdorf, Germany
[2] Univ Mainz, Div Appl Toxicol, Inst Toxicol, D-55131 Mainz, Germany
关键词
DNA repair; O-6 -Methylguanine-DNA methyltransferase (MGMT); apurinic/apyrimidinic endonuclease (APE); long-time kinetics; peripheral blood mononuclear cells;
D O I
10.1007/s002040100226
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
The DNA repair enzymes O-6-methylguanine-DNA methyltransferase (MGMT) and apurinic/apyrimidinic endonuclease (APE, also known as Ref-1) play an important role in cellular defense against the mutagenic and carcinogenic effects of DNA-damaging agents. Cells with low enzyme activity are more sensitive to induced DNA damage and may confer a higher carcinogenic risk to the individuals in question. To study the level of variability of MGMT and APE expression in human, we analyzed in a long-time study MGMT and APE expression in peripheral blood mononuclear cells (PBMC) from healthy individuals. The data revealed high inter- and intraindividual variability of MGMT but high not of APE. For MGMT, the interindividual levels ranged from 27 to 204 fMol/10(6) Cells (7.6-fold, 40 healthy individuals). The intraindividual variation was determined by measuring MGMT repeatedly over 42 days, and was found to vary from 1.4-fold to 3.5-fold. Averaging over the measurement period, some individuals displayed low MGMT activity compared to others. In contrast, APE expression showed only a 2.9-fold difference between individuals and a 1.2 to 2.3-fold intraindividual long-time variation, and thus was less variable than MGMT. MGMT and APE expression were not correlated. Overall the results showed variable MGMT and rather constant APE levels in PBMC of healthy individuals measured over a long period.
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页码:306 / 312
页数:7
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