Detection of primary DNA damage: applicability to biomonitoring of genotoxic occupational exposure and in clinical therapy.
The biological effect of putative genotoxic chemicals in the work place environment was monitored in peripheral mononuclear blood cells of exposed workers. DNA strand breaks, alkali-labile sites of DNA and DNA cross-links were measured using the alkaline filter elution method. A dose dependent increase in DNA damage was found in sterilization workers exposed to ethylene oxide and metal workers with exposure towards N-nitrosodiethanolamine. Two subpopulations with different response to the external exposure were found in nonsmoking sterilization workers. Nurses handling antineo-plastic agents without adequate safety provisions showed a statistically significantly higher rate of DNA strand breaks compared to other nurses handling cytostatic drugs with recommended safety equipment and also compared to not exposed controls. Also in several other occupational groups such as fire fighters possibly exposed to several genotoxic chemicals after an accident in a chemical plant, roofers and petrol pump attendants a significantly higher amount of DNA damage was found compared to controls. No statistically significant differences in the amount of DNA strand breaks were found in cabinet makers and car mechanics compared to controls. In peripheral mononuclear blood cells of ovarial carcinoma patients as well as of patients with Morbus Hodgkin an increased DNA strand break rate was found after application of cytostatic drugs. The individual patients showed a very different response after drug intake. The increase in DNA damage after drug application is possibly related to the success of the chemotherapy.
Oesch
F
F
Institute of Toxicology, University of Mainz, FRG.
Hengstler
J G
JG
Arand
M
M
Fuchs
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity; D002273:Carcinogens; D002460:Cell Line; D004247:DNA / Q000032:analysis / Q000097:blood*; D004249:DNA Damage; D004052:Diethylnitrosamine / Q000031:analogs & derivatives; D004784:Environmental Monitoring; D005027:Ethylene Oxide; D005260:Female; D006689:Hodgkin Disease / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D008297:Male; D009726:Nurses; D016273:Occupational Exposure; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D013242:Sterilization
D000970:Antineoplastic Agents; D002273:Carcinogens; C014129:N-nitrosodiethanolamine; D004052:Diethylnitrosamine; D004247:DNA; D005027:Ethylene Oxide