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Biomedical subjects

M Sorsa

Publications and source records attributed to M Sorsa.

At least 91 records · Page 5Linked to original sources

Monitoring of sister chromatid exchange and micronuclei as biological endpoints.

Cytologically visible damage in human chromosomes can be detected as structural chromosomal aberrations, numerical changes in genome, sister chromatid exchanges (SCE) or as micronucleated cells. The importance of in-vivo cytogenetic damage that is induced in human cells is that it indicates that similar alterations may have occurred in other tissues, either in somatic or in germinal cells. SCEs represent symmetrical exchanges between sister chromatids; generally, they do not result in alteration of the chromosome morphology or the genetic information. Although the detection method is highly sensitive as an in-vitro screening test, in monitoring studies, it seems to be restricted to cases where the exposing agents are strong alkylating compounds (e.g., ethylene oxide, cytostatic drugs) or to some multi-exposure conditions (e.g., cigarette smoking, laboratory work, rubber industries). Micronuclei arise from acentric chromosome fragments or lagging whole chromosomes. They have been detected in a variety of dividing human cells, including exfoliated epithelial cells, bone-marrow cells and lymphocytes. Positive responses of induction of cells with micronuclei have been obtained in studies with cells of the buccal mucosa (chewers of betel or tobacco) or cultured lymphocytes of some groups occupationally exposed to agents like styrene or ethylene oxide.

Cell Nucleus↗

Occupational handling of cytostatic drugs.

The bacterial fluctuation test and measurement of the frequency of sister chromatid exchanges were used for evaluation of the exposure of different groups of hospital personnel to cytostatic drugs. Increased mutagenic activity in the urine was detected only in personnel working with inadequate safety precautions, e.g., lack of a ventilated safety cabin for preparation of parenteral solutions. Although such a safety cabin was used within the hospital pharmacy, increased mutagenic activity was detected in the urine of prescriptionists preparing parenteral cytostatic drugs. After a change of glove material and improvement of ventilation in the safety cabin, no work-related increase in urinary mutagenic activity was seen. None of the different groups tested, showed any increase in the frequency of sister chromatid exchanges. It is therefore concluded that handling of cytostatic drugs according to the issued safety recommendations including working in a well ventilated safety cabin, will not result in any enhancement of mutagenic activity in the urine related to work.

Adult↗

Urinary excretion of thioethers among low-tar and medium-tar cigarette smokers.

The urinary excretion of thioethers was studied among smokers of medium-tar cigarettes (16.3 mg/cig.) and low-tar cigarettes (5.4 mg/cig.). The test persons (26 smokers and 11 nonsmokers) were healthy young men in the military service. The smokers had an increased excretion of thioethers into the urine (P = 0.002 with Mann-Whitney U-test) when compared with the nonsmokers. No differences in the amount of urinary thioethers were detected between the low-tar and medium-tar cigarette smokers. The smokers (varying from 2.0 to 8.5 mmol/mol creatinine) had more individual variation than the nonsmokers (varying from 1.5 to 4.5 mmol/mol creatinine). Furthermore, the individual variation in the group of low-tar cigarette smokers did not markedly differ from the individual variation of medium-tar cigarette smokers.

Adult↗

Effect of emissions from residential wood stoves on SCE induction in CHO cells.

The SCE-induction capacity of emissions from an airtight horizontal baffled residential wood stove was investigated in CHO cells. The samples were taken under normal and starved air conditions, from burning birch and spruce separately. Both particle phase and vapour phase were collected. All samples induced a dose-related response in SCE both with and without a metabolic activation system, the rat-liver microsomal fraction. The burning conditions in the stove influenced the mutagenicity of the emissions more than the type of wood; the smoke from wood burning under starved air conditions was more than one order of magnitude more potent in inducing a significant SCE response. With all samples, the response in SCE induction was highest without metabolic activation. The toxicity of the samples, especially those without S9, limited the dose-range tested.

Animals↗

Genotoxic hazards in the rubber industry.

The toxicology of chemicals used in the rubber industry is poorly known. In the present investigation an attempt was made to use biological monitoring methods to identify job categories with possible exposure to potentially genotoxic chemicals. Urine samples were collected and analyzed for mutagenic activity by the bacterial fluctuation test. The highest individual mutagenic activities were detected among the workers in the weighing and mixing departments, and some high individual values were found among vulcanizers. Sister chromatid exchanges (SCE) and structural chromosome aberrations were also analyzed from samples of peripheral blood. The effect of smoking was clearly associated with significantly increased numbers of SCEs and chromosome aberrations. Among the workers in different job categories, the highest SCE frequencies were found for mixers who smoked. Also nonsmoking cleaners of the mixing department differed significantly from the nonsmoking referents in this respect. However, only the group of nonsmoking weighers showed an increase in the number of chromosome aberrations (p less than 0.01) when compared with the referents. The results suggest the need for improved occupational hygiene in the weighing and mixing departments of rubber plants so that exposure to potentially hazardous genotoxic chemicals can be decreased.

Chromosome Aberrations↗

Biological monitoring in surveillance of exposure to genotoxicants.

Biological monitoring comprises analysis of samples taken of individuals with presumed or known exposures in order to estimate either the body uptake of a toxicant or to detect reversible effects of the exposure. In medical surveillance, biological monitoring is a preventive tool whose function is either to identify the hazardous exposures, or the early biological effects of such exposures. Biological monitoring is of special importance in identifying exposures to genotoxicants, for which no safe thresholds are known and the effects of which are prone to large interindividual variations. Both the uptake of the genotoxicant(s) and their biological effect should be considered determinants of the hazard potential of the exposure. Thus the occurrence of either one of these phenomena is a reason for preventive health measures.

Alkylating Agents↗

A chromosome study among worker groups in the rubber industry.

Two cytogenetic endpoints, structural chromosome aberrations and sister chromatid exchanges, were analyzed in the blood lymphocytes of several worker groups and referents for an evaluation of possible work-related exposures to chromosome-damaging agents. A total of 35 referents and 55 rubber workers, the latter representing six job categories in two rubber factories, were included in the study. The two job categories frequently revealing increased sister chromatid exchanges or chromosome aberrations were mixers and weighers of chemicals. Statistically significantly increased sister chromatid exchange values were found among the weighers and the mixers. When chromosome aberrations were analyzed, only the group of nonsmoking weighers showed significantly higher values than the reference group. Smoking was found to correlate with increased frequencies of sister chromatid exchanges and chromosome aberrations among both the workers and the referents.

Adult↗

Metabolic activation of styrene by erythrocytes detected as increased sister chromatid exchanges in cultured human lymphocytes.

Styrene induces sister chromatid exchanges (SCEs) in human whole-blood lymphocyte cultures without exogenous metabolizing systems, which indicates that styrene is metabolically activated in this in vitro system. Whole-blood lymphocyte cultures from 11 male donors showed a clear increase in SCEs after a 48-hr treatment with styrene (2 mM) or with the reactive metabolite styrene 7,8-oxide (0.15 mM). Styrene (0.5 to 4 mM) induced a distinct dose-dependent increase of SCEs in whole-blood cultures (with 200 to 400 million red blood cells/ml) but only a slight effect in purified lymphocyte cultures (with 20,000 red blood cells/ml). SCE induction by styrene (2 mM) depended on the amount of red blood cells (0.02 to 2000 million/ml) added to the purified lymphocyte cultures. Cyclophosphamide, studied for comparison, clearly increased SCEs irrespective of the presence of erythrocytes. The results show that erythrocytes are essential for the activation of styrene in the lymphocyte test system. This activation probably results from the conversion of styrene into styrene 7,8-oxide by oxyhemoglobin.

Biotransformation↗

Biologic monitoring of exposure to chemical mutagens in the occupational environment.

Occupational exposure to chemical mutagens can be monitored by measuring the chemical interaction that occurs between the exposing agent and biologic macro-molecules. Such interaction is detectable in the body fluids as adducts of, e.g., DNA or glutathione. The mutagenic compounds or their metabolites can also be measured from urine samples, by use of bacterial mutagenicity assays. Much basic research is still needed before these methodologies are applicable for routine monitoring. At present, cytogenetic approaches appear to be nearest to routine surveillance in detecting early biologic effects in exposed humans. Studies on structural chromosome aberrations or sister chromatid exchanges (SCEs) in peripheral blood lymphocytes obviously detect different molecular injuries, and the results from in vivo occupational exposures do not necessarily correlate. Somatic chromosome damage should always be considered a warning sign of potentially adverse effects, and such damage should lead to decreased exposure to the causative agent.

Chromosome Aberrations↗

Identification of mutagen exposures in the rubber industry by the sister chromatid exchange method.

The rubber industry is known to use a large and expanding array of chemicals, some of which are experimentally proven mutagens or carcinogens. An association with cancer risk has been shown in several epidemiological studies carried out in the rubber industry. Sister chromatid exchanges were studied in blood lymphocytes of 54 workers from various job categories in two rubber plants and 34 control subjects mainly from office jobs. The highest numbers of SCEs were observed among rubber workers who smoked, but smokers in the control group also differed significantly from non-smokers by their incidence of SCEs. In both rubber plants the highest incidence of SCEs was observed among workers employed in the mixing operations of the rubber chemicals.

Adult↗

A chromosome study among stainless steel welders.

The mutagenicity of welding fumes generated by manual metal arc (MMA) welding of stainless steel (SS) has been shown in several experimental in vitro systems. No data are available on possible chromosome damage among MMA/SS welders. In the present study, structural chromosome aberrations and sister chromatid exchanges (SCEs) were studied in peripheral blood lymphocytes of 23 welders and 22 control subjects. No significant differences in the frequency of chromosome aberrations or SCEs were detected between the two groups. Smokers, both welders and controls, showed a significantly higher SCE rate than non-smokers.

Adult↗

Possibilities for identifying genotoxic risks in the rubber industry: use of the urinary mutagenicity assay and sister chromatid exchange.

Two approaches have been used for biological monitoring of exposure to genotoxins in the rubber industry: (1) assay of mutagenic activity in urine with the bacterial fluctuation test; and (2) analysis of sister chromatid exchange frequencies in peripheral blood lymphocytes. Workers in the rubber industry have significantly more mutagenic activity in their urine than nonexposed controls. Mutagenic activity was tested with Escherichia coli WP2 uvrA as indicator bacteria was significantly higher in urine of workers after a normal work week than in urine samples from the same individuals after a holiday. The mean frequency of sister chromatid exchange in rubber workers who smoked was significantly higher (p less than 0.01) than that in unexposed smokers. The only job categories in which workers who smoked had statistically significantly higher mean frequencies than others were mixing and weighing. People in these jobs generally also had high mutagenic activity in their urine.

Female↗