Relevance of environmental alkylating agents to repair protein O6-alkylguanine-DNA alkyltransferase: determination of individual and collective repair capacities of O6-methylguanine.
The repair capacity for O6-methylguanine was determined in cell homogenates of peripheral blood lymphocytes of 35 automobile industry workers, exposed to rubber and tires, and of 35 clinical workers, handling cancer chemotherapeutic agents, compared to control groups. lambda-Phage DNA containing one 32P-labeled O6-methylguanine in each BamHI site was used as substrate for the repair protein O6-alkylguanine-DNA alkyltransferase (AGT). The clinical personnel showed in the mean a highly significantly (P = 0.0014, Wilcoxon U test, Mann and Whitney) reduced activity of the repair enzyme [3.28 +/- 0.28 (SEM) fmol AGT/micrograms DNA] as compared to 37 control persons (4.88 +/- 0.32 fmol AGT/micrograms DNA). The mean AGT value of the automobile industry workers (4.40 +/- 0.28 fmol AGT/micrograms DNA) was not significantly different (P = 0.1303) from the mean of 38 examined controls (5.00 +/- 0.28 fmol AGT/micrograms DNA). By dividing these employees into subgroups according to their different work environments (handling of rubber fittings, tire mounting, and tire storage, respectively) the mean AGT value of the 15 tire storage workers was significantly (P = 0.0270) lower (3.80 +/- 0.36 fmol AGT/micrograms DNA) than the mean value of the controls. The interindividual variations in the activity of AGT were 5.1- and 6.5-fold in the control groups and 5.6-fold for the automobile industry workers; the largest variations were found in the group of the clinical personnel with 12.6-fold. No significant correlations between AGT and age, sex, or smoking behavior were observed in any of the groups examined. The decrease in AGT activity will render the afflicted individuals more susceptible to further exposure to methylating agents.
Oesch
F
F
Institute of Toxicology, University of Mainz, Germany.
Klein
S
S
D001336:Automobiles; D010582:Bacteriophage lambda; D004260:DNA Repair; D004279:DNA, Viral / Q000378:metabolism; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D008780:Methyltransferases / Q000378:metabolism*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D009790:Occupations; D010761:Phosphorus Radioisotopes; D012016:Reference Values; D013379:Substrate Specificity
D004279:DNA, Viral; D010761:Phosphorus Radioisotopes; D006147:Guanine; C008449:O-(6)-methylguanine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase