The DNA repair enzymes O6-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 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 intra-individual 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.

A recent study reported that exposure of student embalmers in Cincinnati to high concentrations of formaldehyde (2 mg/m3) reduced the activity of the DNA repair protein O6-methylguanine DNA methyltransferase (MGMT). Reduction in a DNA repair enzyme may strongly increase the cancer risk not only with respect to the repair-enzyme causing agent but with respect to all carcinogens causing lesions subject to repair by the enzyme in question. Thus, we examined whether formaldehyde exposure of 57 medical students during their anatomy course at two different Universities in Germany influenced MGMT activity in mononuclear blood cells. Mean formaldehyde exposure of 41 students was 0.2 +/- 0.05 mg/m3 for 6 h per week. MGMT activity was 133.2 +/- 14.9 fmol MGMT/10(6) cells before the beginning of the formaldehyde exposure, 131.1 +/- 15.8 fmol MGMT/10(6) cells after 50 days (P = 0.56) and 128.2 +/- 19.0 fmol MGMT/10(6) cells after 111 days of exposure (P = 0.92). Similarly, no significant influence of formaldehyde exposure was observed, when smoking habits, alcohol consumption, allergic disease and sex of students were considered. In addition no significant difference was obtained in MGMT activity between 16 students with mean formaldehyde exposure of 0.8 +/- 0.6 mg/m3 and students without formaldehyde exposure (n = 51; P = 0.37). In conclusion, exposure of the medical students in western Europe to formaldehyde did not decrease MGMT activity in mononuclear blood cells.