0000000000735607
AUTHOR
Kai Janssen
Long-time expression of DNA repair enzymes MGMT and APE in human peripheral blood mononuclear cells.
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 inter…
Guanine 6-O-Methylation Pattern within the Dioxin Responsive Element of theCYP1A1 Enhancer Shows Two Critical Guanines for AhR/ARNT Binding
The core-recognition motif for TCDD-liganded AhR/ARNT complex of the dioxin-responsive element (DRE) contains four guanine residues, three on the antisense (5'-T T / A GCGTG-3') and one on the sense (5'-CACGC A / T A-3') strand. It has been reported that, in methylation-protection and methylation-interference assays, the TCDD-liganded AhR/ARNT contacts all four guanine residues. On the other hand, it is known that some anticancer drugs, and various environmental and workplace chemicals, including strongly human carcinogenic nitrosoamines, lead to the highly miscoding 6-O-methylation of guanine. In the present study, we have investigated whether specific methylation of guanine at the 6-O-pos…
DNA repair activity of 8-oxoguanine DNA glycosylase 1 (OGG1) in human lymphocytes is not dependent on genetic polymorphism Ser326/Cys326.
8-oxoguanine DNA glycosylase 1 (OGG1) is a DNA repair enzyme that excises 7,8-dihydro-8-oxoguanine (8oxoG) from DNA. Since 8oxoG is a highly mispairing lesion, decreased OGG1 expression level could lead to a higher background mutation frequency and could possibly increase the cancer risk of an individual under oxidative stress. In order to analyse the natural variation of OGG1, we measured the DNA repair activity in human lymphocytes of healthy individuals by means of an 8oxoG-containing oligonucleotide assay. The data obtained revealed a two fold interindividual variation of OGG1 activity in lymphocytes. There was no difference in OGG1 activity due to gender and smoking behaviour. Transcri…