DNA single strand breaks, including DNA adducts that lead to alkali-labile sites, were measured in peripheral mononuclear blood cells of 35 petrol pump attendants by alkaline filter elution. Blood samples from petrol pump attendants were taken on Monday and Friday. Additionally, DNA single strand breaks of smoking and non-smoking control persons were examined. For the smoking (n = 12) and the non-smoking controls (n = 20) a mean normalized elution rate of 1.49 +/- 0.52 (mean value +/- 95% confidence interval) and 1.32 +/- 0.28, respectively, was obtained. The difference between smoking and non-smoking controls was not statistically significant (U test). An increase in DNA single strand breaks from Monday to Friday was detected for non-smoking petrol pump attendants with a daily working time of more than 4 h at the pump station. Their mean normalized elution rate increased from 1.08 on Monday to 1.89 on Friday. This difference was statistically significant (P < 0.05; Wilcoxon test for paired data), although the 95% confidence interval was large on Friday (0.43 on Monday; 1.23 on Friday). However, no significant increase was found for non-smoking petrol pump attendants who were on duty for less than 4 h per day at the pump station. No statistically significant increase in DNA single strand breaks could be detected for smoking petrol pump attendants whether they were pumping gasoline for more or for less than 4 h per day.
Bay region diolepoxide-DNA adducts of dibenz[a,h]anthracene (DBA) formed in vitro were identified and their absolute stereochemistry was assigned. After activation of [5,12-14C]DBA with liver microsomes obtained from Aroclor 1254 treated male Sprague-Dawley rats in the presence of calf thymus DNA for 1 h, the amount of DNA adducts was found to be 9.9 +/- 2.4 pmol/mg DNA, calculated on the basis of the portion of radioactivity eluted from the HPLC reversed-phase column with a water/acetonitrile gradient. Bay region diolepoxide-DNA adducts represented 27.5% of radioactivity associated with DNA adducts. The absolute configuration of the various adducts was determined from the reaction of the (+)- and (-)-3,4-dihydrodiol after metabolic activation and the reaction of the anti- and syn-3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrodibenz[a,h]anthracen e with DNA or with the individual deoxyribonucleotides. The main bay region adduct was identified as a deoxyguanosine adduct of (anti)-3S,4R-dihydroxy-1R,2S-epoxy-1,2,3,4-tetrahydrodibenz [a,h]anthracene, a metabolite of (-)-3,4-dihydroxy-3,4-dihydrodi- benz[a,h]anthracene. Anti bay region diolepoxide-deoxyguanosine adducts of DBA contributed to 17.7% and syn diolepoxide-derived deoxyguanosine adducts to 5.8% of adduct-associated radioactivity. The amount of bay region deoxyadenosine adducts was calculated to be 4%. For six of probably eight different deoxyadenosine adducts absolute stereochemistry could be assigned. 32P-Postlabelling experiments revealed a binding of 23 +/- 6 pmol/mg DNA for (-)-3,4-dihydrodiol and of 1.5 +/- 0.4 pmol/mg DNA for (+)-3,4-dihydrodiol of DBA.
Objectives The aim of the study was to detect single-strand breaks in deoxyribonucleic acid (DNA) in ~noilonuclear blood cells of fire fighters exposed to o-nitroanisole and other substances released into the environment during an accident in a chemical plant. Methods The level of DNA single-strand brealts in mononuclear blood cells was detected by alkaline elution. The results were compared for 16 fire fighters who worked in a contaminated area for about 8 h and two reference groups (one of fire fighters who had not worlted in the conta~llinated area, group I, and one of persons without any apparent occupational exposure to genotoxic substances, group 11). Results The mean nonnalized elution rate (nER) 19 d after the accident was slightly but statistically significantly (P < 0.05) higher for the exposed fire fighters [mean 1.48 k 95% confidence interval (95% CI) 0.211 than for reference group I (mean 1.21 f 95% CI 0.21) or reference group 11 (mean 1.17 k 95% CI 0.18). No statistically significant difference was found between reference groups 1 and 11. Another analysis was performed three months after the first. The level of DNA single-strand breaks (mean nER 1.12 k 95% CI 0.1 I) was no longer increased in comparison with the levels of the reference groups. C O~~C~U S~O~~S DNA single-strand breaks were increased in fire fighters exposed to o-nitroanisole and other substances. In comparison with the extent of DNA strand brealts found in other occupational groups the increase was only moderate. The observed decrease in DNA single-strand breaks to the reference level in exposed fire fighters three months later suggests a DNA repair mechanism for DNA single-strand brealts caused by o-nitroanisole. Key terms acute toxicity, biomonitoring, DNA single-strand breaks, fire fighters, hutnan rnononuclear blood cells, o-nitsoanisole.
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.
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