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

The DNA repair enzymes O-6-methylguanine-DNA methyltransferase (MGMT) and a purinic/apyrimidinic endonuclease (APE, also known as Ref-1) play an import ant 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 indi viduals in question. To study the level of variability of MGMT and APE expr ession in human, we analyzed in a long-time study MGMT and APE expression i n peripheral blood mononuclear cells (PBMC) from healthy individuals. The d ata revealed high inter- and intraindividual variability of MGMT but high n ot of APE. For MGMT, the interindividual levels ranged from 27 to 204 fMol/ 10(6) Cells (7.6-fold, 40 healthy individuals). The intraindividual variati on 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, s ome 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 va riable than MGMT. MGMT and APE expression were not correlated. Overall the results showed variable MGMT and rather constant APE levels in PBMC of heal thy individuals measured over a long period.