Professional and public attitudes towards unsolicited medical intervention.
Explore the source record for details and available documents.
Accidents, Traffic↗
Biomedical subjects
L E Knudsen
Publications and source records attributed to L E Knudsen.
Biomarkers for exposure to ambient air pollution--comparison of carcinogen-DNA adduct levels with other exposure markers and markers for oxidative stress.
Human exposure to genotoxic compounds present in ambient air has been studied using selected biomarkers in nonsmoking Danish bus drivers and postal workers. A large interindividual variation in biomarker levels was observed. Significantly higher levels of bulky carcinogen-DNA adducts (75.42 adducts/10(8) nucleotides) and of 2-amino-apidic semialdehyde (AAS) in plasma proteins (56.7 pmol/mg protein) were observed in bus drivers working in the central part of Copenhagen, Denmark. In contrast, significantly higher levels of AAS in hemoglobin (55.8 pmol/mg protein), malondialdehyde in plasma (0. 96 nmol/ml plasma), and polycyclic aromatic hydrocarbon (PAH)-albumin adduct (3.38 fmol/ microg albumin) were observed in the suburban group. The biomarker levels in postal workers were similar to the levels in suburban bus drivers. In the combined group of bus drivers and postal workers, negative correlations were observed between bulky carcinogen-DNA adduct and PAH-albumin levels (p = 0.005), and between DNA adduct and [gamma]-glutamyl semialdehyde (GGS) in hemoglobin (p = 0.11). Highly significant correlations were found between PAH-albumin adducts and AAS in plasma (p = 0.001) and GGS in hemoglobin (p = 0.001). Significant correlations were also observed between urinary 8-oxo-7, 8-dihydro-2'-deoxyguanosine and AAS in plasma (p = 0.001) and PAH-albumin adducts (p = 0.002). The influence of the glutatione S-transferase (GST) M1 deletion on the correlation between the biomarkers was studied in the combined group. A significant negative correlation was only observed between bulky carcinogen-DNA adducts and PAH-albumin adducts (p = 0.02) and between DNA adduct and urinary mutagenic activity (p = 0.02) in the GSTM1 null group, but not in the workers who were homozygotes or heterozygotes for GSTM1. Our results indicate that some of the selected biomarkers can be used to distinguish between high and low exposure to environmental genotoxins.
Adult↗
Chromosomal aberrations in humans induced by urban air pollution: influence of DNA repair and polymorphisms of glutathione S-transferase M1 and N-acetyltransferase 2.
We have studied the influence of individual susceptibility factors on the genotoxic effects of urban air pollution in 106 nonsmoking bus drivers and 101 postal workers in the Copenhagen metropolitan area. We used the frequency of chromosomal aberrations in peripheral blood lymphocytes as a biomarker of genotoxic damage and dimethylsulfate-induced unscheduled DNA synthesis in mononuclear WBCs, the glutathione S-transferase M1 (GSTM1) genotype, and the N-acetyltransferase 2 (NAT2) genotype as biomarkers of susceptibility. The bus drivers, who had previously been observed to have elevated levels of aromatic DNA adducts in their peripheral mononuclear cells, showed a significantly higher frequency of cells with chromosomal aberrations as compared with the postal workers. In the bus drivers, unscheduled DNA synthesis correlated negatively with the number of cells with gaps, indicating a protective effect of DNA repair toward chromosome damage. Bus drivers with the GSTM1 null and slow acetylator NAT2 genotype had an increased frequency of cells with chromosomal aberrations. NAT2 slow acetylators also showed elevated chromosomal aberration counts among the postal workers. Our results suggest that long-term exposure to urban air pollution (with traffic as the main contributor) induces chromosome damage in human somatic cells. Low DNA repair capacity and GSTM1 and NAT2 variants associated with reduced detoxification ability increase susceptibility to such damage. The effect of the GSTM1 genotype, which was observed only in the bus drivers, appears to be associated with air pollution, whereas the NAT2 genotype effect, which affected all subjects, may influence the individual response to some other common exposure or the baseline level of chromosomal aberrations.
Adult↗
Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH).
Chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), and micronuclei (MN) in peripheral blood lymphocytes have for decades been used as cytogenetic biomarkers to survey genotoxic risks in the work environment. The conceptual basis for this application has been the idea that increased cytogenetic damage reflects an enhanced cancer risk. Nordic and Italian cohorts have been established to evaluate this hypothesis, and analyses presented previously have shown a positive trend between CA frequency and increased cancer risk. We now report on a pooled analysis of updated data for 3541 subjects examined for CAs, 2703 for SCEs, and 1496 for MN. To standardize for interlaboratory variation, the results for the various cytogenetic end points were trichotomized on the basis of the absolute value distribution within each laboratory as "low" (1-33 percentile), "medium" (34-66 percentile), or "high" (67-100 percentile). In the Nordic cohort, there was an elevated standardized incidence ratio (SMR) for all cancer among subjects with high CA frequency [1.53; 95% confidence interval (CI), 1.13-2.05] but not for those with medium or low CA frequency. In the Italian cohort, a SMR in cancer of 2.01 (95% CI, 1.35-2.89) was obtained for those with a high CA frequency level, whereas the SMRs for those with medium or low did not noticeably differ from unity. Cox's proportional hazards models gave no evidence that the effect of CAs on total cancer incidence/mortality was modified by gender, age at test, or time since test. No association was seen between the SCEs or the MN frequencies and subsequent cancer incidence/mortality. The present study further supports our previous observation on the cancer predictivity of the CA biomarker, which seems to be independent of age at test, gender, and time since test. The risk patterns were similar within each national cohort. This result suggests that the frequency of CAs in peripheral blood lymphocytes is a relevant biomarker for cancer risk in humans, reflecting either early biological effects of genotoxic carcinogens or individual cancer susceptibility.
Chromosome Aberrations↗
[Unnecessary medical interventions. A questionnaire study among physicians and laymen].
The aim of the study was to survey attitudes among medical doctors and lay people to unsolicited medical intervention. The design of the study was an anonymous questionnaire study including three scenarios implying ethical considerations. A total of 445 medical doctors working within different areas received the questionnaire, as did 75 medical students and 600 lay people. The results showed a response rate of 67%, highest among medical doctors and students. The lay people had significantly higher expectations concerning the medical intervention in two out of three scenarios compared to medical doctors and students. The participants were offered the opportunity to comment on the questionnaire. The conclusion of the Danish survey is that there is a significantly different approach to unsolicited medical intervention among lay people compared to medical doctors and students. Medical doctors are less disposed to perform unsolicited intervention compared with the wishes/expectations of the lay people. More open attitudes and information as well as better communication is recommended.
Aged↗
DNA damage in isolated rat hepatocytes exposed to C.I. pigment orange 5 and C.I. pigment yellow 12 by the alkaline comet assay.
The induction of DNA damage by commonly used printing ink pigments, C.I. pigment orange 5 (C.I. 12075) and C.I. pigment yellow 12 (C.I. 21090), was investigated in freshly isolated rat hepatocytes with the comet assay. C.I. pigment yellow 12 is a 3,3'-dichlorobenzidine-based diarylide pigment, and C.I. pigment orange 5 is a naphthol-azo pigment. The pigments are virtually insoluble in aqueous solutions, and they have not been tested extensively for toxicological effects. C.I. pigment orange 5 increased the levels of DNA damage at 5 microg/ml (P < 0.02) and C.I. pigment yellow 12 at 20 microg/ml (P < 0.002). The effect of incubation time (20, 40, and 80 min) of the same concentrations of the pigments was tested. The levels of DNA damage were increased up to 80 min. Both pigments produced DNA damage that was in the same range as the food carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline. Our data indicate that both C.I. pigment orange 5 and C.I. pigment yellow 12 are genotoxic in hepatocytes with metabolizing capacities. However, further investigation of the metabolism and disposition are required for the evaluation of the safety of these pigments.
Alkalies↗
Seasonal variation of DNA damage and repair in patients with non-melanoma skin cancer and referents with and without psoriasis.
Quadruples of skin cancer patients with and without psoriasis and referents with and without psoriasis (4 x 20 study persons) were identified and examined for DNA damage by single cell gel electrophoresis (comet-assay) and DNA-repair by UV-induced unscheduled DNA synthesis (UDS) in mononuclear blood cells (lymphocytes and monocytes). DNA damage (strand breaks and alkaline labile sites) as assessed by the comet assay and DNA repair as assessed by UDS were significantly associated with the season in which blood sampling took place. This variation might be explained by an increased exposure to solar radiation. When the comet tail moment data were stratified by sampling period, an interaction between psoriasis and skin cancer was detected, with patients with psoriasis and skin cancer exhibiting more DNA damage. Patients with psoriasis and skin cancer also had lower UDS compared to healthy study persons, suggesting that the more DNA damage may be caused by a lower rate of DNA repair. In all study persons, the extent of UDS correlated positively with the amount of DNA damage determined by the comet assay.
Blood Cell Count↗
Analysis of native human plasma proteins and haemoglobin for the presence of bityrosine by high-performance liquid chromatography.
Generation of reactive oxygen species in vivo results in oxidative-damage to cellular components, including proteins. Due to the relatively long half-lives of several blood proteins the cumulative formation of oxidatively damaged proteins might serve as a biomarker for reactive oxygen species formation. The most prominent sources of reactive oxygen species in vivo are site-specific metal ion-catalyzed reactions of the Fenton and Haber-Weiss types and the H2O2/peroxidase system. In vitro oxidation of L-tyrosine using a peroxidase or Cu++/H2O2 system gives rise to the formation of a highly fluorescent substance, bityrosine. High-performance liquid chromatography (HPLC) analysis of acid hydrolyzed serum albumin after oxidation with peroxidase/H2O2 or with Cu++/H2O2 showed that bityrosine had been formed whereas oxidation of this protein with Fe(III)/ascorbate did not result in the formation of bityrosine. Bityrosine could not be detected in human plasma proteins or haemoglobin with the detection limit of one pmol per mg protein.
Adult↗
Oxidative stress associated with exercise, psychological stress and life-style factors.
Oxidative stress is a cellular or physiological condition of elevated concentrations of reactive oxygen species that cause molecular damage to vital structures and functions. Several factors influence the susceptibility to oxidative stress by affecting the antioxidant status or free oxygen radical generation. Here, we review the effect of alcohol, air pollution, cigarette smoke, diet, exercise, non-ionizing radiation (UV and microwaves) and psychological stress on the development of oxidative stress. Regular exercise and carbohydrate-rich diets seem to increase the resistance against oxidative stress. Air pollution, alcohol, cigarette smoke, non-ionizing radiation and psychological stress seem to increase oxidative stress. Alcohol in lower doses may act as an antioxidant on low density lipoproteins and thereby have an anti-atherosclerotic property.
Air Pollution↗
[Genetic testing in occupational environmental context].
Individuals with an increased risk of occupationally and nonoccupationally induced adverse health effects may be identified by genetic monitoring and genetic screening. Genetic monitoring of induced genetic changes is performed by measurements of chromosomal aberrations or DNA-lesions. Genetic screening includes detection of inherited traits by measurements of enzyme activities in blood, the presence of a specific gene or a specific mutation. Inherited serum alpha-1-antitrypsin deficiency increases the risk of developing a chronic obstructive pulmonary disease. The risk is exacerbated by occupational exposure to dust. The available methods used for genetic screening of individual susceptibility to occupational exposures are not sufficiently validated for routine use. This is especially relevant concerning the population validity referring to how well the markers depict an event in a population. Legal and ethical aspects of preemployment genetic testing are currently discussed in Denmark.
Evaluation Studies as Topic↗
[Genetic measurements in the occupational environment].
Explore the source record for details and available documents.
Denmark↗
Human biological monitoring of occupational genotoxic exposures.
Human biological monitoring is a valuable tool for exposure assessment in groups of persons occupationally exposed to genotoxic agents. If the monitoring activity covers genetic material the term genetic monitoring is used. The methods used for genetic monitoring are either substance specific, e.g. the quantitation of identified DNA-adducts or substance unspecific as is the measurement of DNA-repair. The sample material used for analysis must be well characterized and subject to uniform processing for comparison of the results. Confounding factors of smoking, age and sex must be well controlled for and the biomonitoring results should preferentially be linked with accurate ambient air monitoring. In persons occupationally exposed to styrene the endpoints of DNA-damage and DNA-repair in genetic monitoring are methods of choice in exposure situations above the current Danish (25 ppm) or Finnish (20 ppm) occupational exposure limit value of styrene in ambient air. The consideration of ethical issues in human genetic monitoring is an important but often overlooked aspect. This includes the scientific and preventional relevance of performing a test on individuals, pre- and post study information of donors and confidentiality as well as ownership of the results.
DNA Damage↗
Biomonitoring of genotoxic exposure among stainless steel welders.
A biosurvey in the Danish metal industry measured the genotoxic exposure from stainless steel welding. The study comprised measurements of chromosomal aberrations (CA), sister-chromatid exchanges (SCE), unscheduled DNA synthesis (UDS) in peripheral lymphocytes and serum immunoglobulin G. Environmental monitoring of welding fumes and selected metal oxides, biomonitoring of chromium and nickel in serum and urine and mutagenic activity in urine, and evaluation of semen quality were also done. Manual metal arc (MMA) welding and tungsten inert gas (TIG) welding were the dominant welding processes. A higher frequency of chromosomal aberrations, classified as translocations, double minutes, exchanges and rings, was observed in stainless steel welders than in non-welders. SCE was lower in welders working with both MMA and TIG welding than in reference persons. N-Acetoxy-N-acetylaminofluorene (NA-AAF)-induced UDS was lower in 23 never-smoking welders than in 19 unexposed never-smokers. Smoking was a confounding factor resulting in significantly higher CA, SCE, NA-AAF binding to DNA and mutagenic activity in urine. Age was also a confounder: CA, SCE, NA-AAF binding to DNA and UDS increased significantly with age. No significant correlation between SCE and CA or between CA and UDS was found. UDS decreased significantly with increasing lymphocyte count and a higher lymphocyte count was seen in MMA welders than in reference persons and in smokers than in non-smokers. Differences in the composition among lymphocytes in exposed persons compared with non-exposed are suggested. MMA welding gave the highest exposure to chromium, an increased number of chromosomal aberrations and a decrease in SCE when compared with TIG welding. Consequently improvements in the occupational practice of stainless steel welding with MMA is recommended.
Acetoxyacetylaminofluorene↗
Induction of DNA repair synthesis in human monocytes/B-lymphocytes compared with T-lymphocytes after exposure to N-acetoxy-N-acetylaminofluorene and dimethylsulfate in vitro.
We have explored the induction of DNA repair synthesis in monocyte/B- and T-lymphocyte enriched cell fractions from 12 different human mononuclear blood cell populations. Unscheduled DNA synthesis was measured in monocyte/B- and T-cells after exposure to the DNA-damaging agents dimethylsulfate (DMS) and N-acetoxy-N-acetylaminofluorene in vitro. Also, the binding of DMS to DNA was measured. An increased DNA repair synthesis was measured in monocyte/B-lymphocytes after induction of the two different types of DNA lesions, whereas no induction of unscheduled DNA synthesis was observed in T-lymphocytes. A significantly higher DMS-DNA binding was also observed in monocyte/B-lymphocytes when compared with T-lymphocytes. Specific characterization of mononuclear blood cell populations used in biomonitoring of DNA adducts and repair is recommended.
Acetoxyacetylaminofluorene↗
Stainless steel welding and semen quality.
Questionnaire studies of patients from fertility clinics suggest that welders may have an increased risk of reduced semen quality. In this study, welders and nonwelders from the same plants were asked to provide blood, urine, and semen samples. Urine was analyzed for chromium and nickel, and for mutagenic activity and metal concentration; blood for metal concentrations, immunoglobulin G, total protein, and measures of genotoxicity in lymphocytes; and semen was evaluated by standard semen analysis. Results of the semen evaluation, presented here, showed no difference in semen quality between welders and nonwelders. Because the metal dust exposure of nonwelders in the plant may be higher than that in the general population, welders were also compared to referents not working in the metal industry. Again, no decrease in semen quality associated with welding was demonstrated.
Adult↗
[What do we know about occupational sterility, abortion, and fetal abnormalities?].
Explore the source record for details and available documents.
Abnormalities, Drug-Induced↗