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Biomedical subjects

M Sorsa

Publications and source records attributed to M Sorsa.

At least 73 records · Page 4Linked to original sources
PubMed1988

Mutagenic activity and metabolites in the urine of workers exposed to trinitrotoluene (TNT).

Urine samples taken after work and after a free weekend from 50 workers employed in various activities in a chemical plant manufacturing explosives were analysed. On the basis of hygienic surveys, the subjects were divided into three categories of exposure to trinitrotoluene (TNT). The urine analyses consisted of gas chromatographic identification of TNT and its two metabolites, 4-ADNT and 2-ADNT, and a determination of the mutagenic activity. Two frame shift detector strains of Salmonella typhimurium were used, TA 98 and TA 98 NR, the latter being deficient in endogenous nitroreductase activity. On the basis of previous results on TNT mutagenicity, no exogeneous metabolic system was used to test the urine concentrates. Both tester strains showed that the mean urinary mutagenic activity was higher in the after work samples than in post weekend samples from the same subjects, showing that bacterial nitroreductase activity was not significantly responsible for the mutagenicity, although the response was higher with strain TA 98 than with TA 98 NR. The interindividual variation in urine mutagenicity was high, however, and the difference between the two sampling times was statistically significant (p less than 0.05) only for the high exposed group (workers in trotyl foundry and sieve house). Correlation between urinary mutagenicity and concentration of TNT in urine was poor; correlation was significant only with the urinary concentration of 4-ADNT. The correlation between urinary TNT and both metabolites was good (p less than 0.001). These results suggest that analysis of 4-ADNT in urine would be a sufficient biological measure for controlling exposure to TNT.

Aniline Compounds↗
PubMed1988

Assessment of passive and transplacental exposure to tobacco smoke.

Although tobacco smoke has been shown to be highly genotoxic in various experimental systems, most nonmolecular methods designed to assess exposure to mutagens are too insensitive to detect passive exposure to tobacco smoke. Biochemical markers of intake--cotinine and thiocyanates in body fluids--were shown to be elevated after occupational, passive or transplacental exposure to tobacco smoke, while no response was seen in the frequency of sister chromatid exchanges (SCE) in cultured blood lymphocytes. After occupational exposure to environmental tobacco smoke, the intake marker levels are generally less than 5% of the levels found in active smokers, while cord blood levels (representing fetal exposure) are at about the same level as in the mothers at the time of delivery.

Cotinine↗
PubMed1988

Micronuclei in cytokinesis-blocked lymphocytes as an index of occupational exposure to alkylating cytostatic drugs.

Micronucleated peripheral blood lymphocytes were analysed in cytochalasin-B-treated binucleated lymphocytes using cytocentrifuged preparations. Increased numbers of micronuclei were observed in lymphocytes of groups of workers from industry and hospitals potentially exposed to cyclophosphamide. The finding was independent of the age of the subjects, which was also correlated with micronuclei formation.

Adult↗
PubMed1987

Passive smoking at work: biochemical and biological measures of exposure to environmental tobacco smoke.

Several biochemical and biological measures of tobacco smoke intake were used to evaluate exposure of restaurant personnel to environmental tobacco smoke as compared with active smokers and non-exposed non-smokers. All of the measured parameters--carboxyhaemoglobin (COHb), thiocyanate (SCN) and cotinine in plasma, cotinine and mutagenicity in urine, total white blood cell count (WBC), and sister chromatid exchange (SCE) frequency in cultured lymphocytes--were significantly elevated in the smoker group (n = 22) compared to the non-exposed group (n = 20). Work-related passive exposure (n = 27) was seen most clearly in the cotinine values, both from plasma (mean P-cot in passive smokers 10 ng/ml vs 5.2 ng/ml in non-exposed) and from urine (mean U-cot in passive smokers 56 ng/ml vs 8.3 ng/ml in non-exposed), but significant increases were also seen in the thiocyanate levels (mean P-SNC in passive smokers 58 mumol/l vs 46 mumol/l in non-exposed) and, as a preliminary finding, in total leucocyte count (in passive smokers 8.0 X 10(9)/l vs 6.8 X 10(9)/l in non-exposed). The results demonstrate that environmental tobacco smoke may be an occupational health hazard.

Adult↗
PubMed1987

Effects of exposure to vehicle exhaust on health.

Exposure to combustion engine exhaust and its effect on crews of roll-on roll-off ships and car ferries and on bus garage staff were studied. The peak concentrations recorded for some of the substances studied were as follows: total particulates (diesel only) 1.0 mg/m3, benzene (diesel) 0.3 mg/m3, formaldehyde (gasoline and diesel) 0.8 mg/m3, and nitrogen dioxide (diesel) 1.2 mg/m3. The highest observed concentration of benzo(a)pyrene was 30 ng/m3 from gasoline and diesel exhaust. In an experimental study volunteers were exposed to diesel exhaust diluted with air to achieve a nitrogen dioxide concentration of 3.8 mg/m3. Pulmonary function was affected during a workday of occupational exposure to engine emissions, but it normalized after a few days with no exposure. The impairment of pulmonary function was judged to have no appreciable, adverse, short-term impact on individual work capacity. In the experimental exposure study, no effect on pulmonary function was observed. Analyses of urinary mutagenicity and thioether excretion showed no sign of exposure to genotoxic compounds among the occupationally exposed workers or among the subjects in the experimental study.

Air Pollutants↗
PubMed1986

No difference between urinary mutagenicity in smokers of low-tar and medium-tar cigarettes: a double-blind cross-over study.

Urinary mutagenicity, blood carboxyhemoglobin and serum thiocyanate levels were measured in young, healthy volunteers smoking a fixed number of either low-tar (5 mg/cig.) or medium-tar (15 mg/cig.) cigarettes. The experiment was performed in a double-blind cross-over fashion. The volunteers were under daily control, and their diet and environment were standardized. The urinary mutagenic activity responded dose-dependently to the number of cigarettes smoked (0, 5, 10 or 20 per day), but there was no difference between the smokers of low-tar and medium-tar cigarettes. Neither were any significant differences found in blood carboxyhemoglobin nor serum thiocyanate. These results suggest that there is no substantial difference between the low-tar and medium-tar cigarette as to the inhalation of hazardous compounds in the real smoking situation.

Adult↗
PubMed1986

Genotoxicity and polynuclear aromatic hydrocarbon analysis of environmental tobacco smoke samples from restaurants.

Acetone-extracted samples of airborne particulate matter collected in three restaurants were analysed for their content of polynuclear aromatic hydrocarbons (PAH) and related polynuclear aromatic compounds (PAC) as well as for genotoxic activity using the Salmonella/microsome assay (strains TA98 and TA100) and sister chromatid exchange (SCE) induction in Chinese hamster ovary (CHO) cell cultures. The total particulate matter varied considerably in the restaurants, being 1.37 mg/m3 at the highest; in the same restaurant the highest amount of total PAHs (168 ng/m3) was also detected. Altogether, 13-22 individual PACs were identified in the samples, ranging from phenanthrene to benzothionaphthene. All of the six samples caused significant increases both in bacterial revertant and SCE frequencies. In the Salmonella assay, the mutagenic activity detected was primarily with metabolic activation. However, in the CHO cell cultures the induction of SCEs was also seen without an exogenous metabolic activation system. The cytotoxicity of the extracts limited the concentration range tested in the SCE assay. Only a partial correspondence of the total PAH content with the genotoxic activity of the samples was found. The genotoxicity of restaurant air exceeded by one to two orders of magnitude the previously reported activities detected by similar methods in urban outdoor and indoor air samples.

Animals↗
PubMed1985

Occupational exposure to anticancer drug--potential and real hazards.

Many anticancer agents have been shown to be mutagenic, teratogenic and carcinogenic in experimental systems and second malignancies are known to be associated with several specific therapeutic treatments. Anticancer agents thus represent a class of occupational carcinogens, the handling of which should involve no unnecessary exposure. The available methodologies to detect possible exposures from ambient air and from biological samples are discussed, and the published data on results are reviewed. Analytical methods are available for the detection of most frequently used anticancer drugs from all groups, i.e., alkylating agents, mitotic inhibitors, antimetabolites and antibiotics. The ambient samples taken from sites of admixture of cytostatics have often shown detectable, but low concentrations of anticancer agents. Urine samples from patients under chemotherapy as well as from personnel handling the drugs occupationally in hospitals have been analyzed both chemically and for excreted mutagenicity. Both cisplatin and cyclophosphamide have been detected in the urine of patients; furthermore, cyclophosphamide was observed in the urine of nurses who formulate and deliver this drug. Urinary mutagenicity assays have given both positive and negative results in various groups of nursing and pharmacy personnel. Cytogenetic methods have, likewise, been applied for monitoring purposes. Most of the available data concerns chromosome aberrations (CA) or sister-chromatid exchanges (SCE) induced in peripheral blood lymphocytes of patients under chemotherapy. A few studies on groups occupationally exposed to anticancer drugs have given positive results, but also negative reports have appeared for these same cytogenetic parameters. No studies are as yet available on the possible carcinogenic effects of occupational handling of anticancer drugs. Two recent case-referent studies among hospital personnel have pointed to slightly increased risks of disorders in pregnancy outcome; one of the studies has shown an excess of spontaneous abortions and other malformations in children of females with a history of work with anticancer agents.

Abnormalities, Drug-Induced↗
PubMed1985

Passive and active exposure to cigarette smoke in a smoking experiment.

Six volunteer female habitual smokers were exposed during a 2-wk experimental period to cigarette smoke, both actively and passively, in an exposure chamber (volume 10 m3, average air exchange rate 6.8 times/h), where the ambient carbon monoxide, particle, and aldehyde concentrations were monitored. Three of the six subjects were smoking at the time, 2 cigarettes (filtered, self-burning low tar brand) per person per hour, 30 cigarettes altogether during each of the 5-h experimental days in the chamber. Samples of blood and urine were taken from each subject after 3 nonsmoking days and after each day of active or passive smoking. Among the parameters tested, blood carboxyhemoglobin, plasma cotinine, and urinary mutagenicity were higher in samples taken after active smoking than after nonsmoking periods. Although the exposure conditions were similar for all subjects, the parameters measured showed quite high interindividual variation. Thioethers and thiocyanates were not significantly elevated in the active smoking samples; neither were there any differences during this short experimental period in the sister chromatid exchange frequencies. The only parameters showing an increasing trend after passive exposure, as compared with nonsmoking samples, were urinary mutagenicity and plasma cotinine, the main metabolite of nicotine.

Adult↗
PubMed1985

Urinary screening for potentially genotoxic exposures in a chemical industry.

Mutagenic activity, measured by the bacterial fluctuation assay and thioether concentration in urine from workers at a chemical plant producing pharmaceuticals and explosives, was determined before and after exposure. Of 12 groups only those exposed to trinitrotoluene (n = 14) showed a significant increase in mutagenic activity using Salmonella typhimurium TA 98 without any exogenous metabolic system. The same strain responded only weakly when the S-9 mix was used; with Escherichia coli WP2 uvrA no effect of exposure was observed. Urinary thioether concentration was higher among smokers than among non-smokers, but occupational exposure had no effect. Urinary mutagenicity testing may be a useful tool for screening potentially genotoxic exposures in complex chemical environments.

Chemical Industry↗
PubMed1984

Sister chromatid exchanges and chromosome aberrations in rubber workers.

Sister chromatid exchanges and chromosomal aberrations were studied in peripheral blood lymphocytes of 55 rubber workers (from two different plants) and 35 controls mainly employed in office jobs. In both plants an increased frequency of SCEs (P less than 0.05 for plant A and P less than 0.01 for plant B) was detected in nonsmoking rubber workers as compared with nonsmoking referents. When the SCEs of worker groups belonging to the different job categories were compared with referents, the only groups showing statistically significant increases in SCEs were the smoking workers from the weighing and mixing departments of factory A and the nonsmoking weighers of factory B. A slight increase in the SCE frequencies was seen especially among smoking workers employed in the chemical mixing departments. The frequency of structural chromosome aberrations was not significantly increased in the occupational groups studied, the only exception being the small group of nonsmoking weighers in plant B. Among both the exposed workers and the controls, smokers had a higher mean SCE frequency than nonsmoking referents. This difference was significant between the exposed smokers and nonsmokers of plant A (P less than 0.01) and between smoking and nonsmoking controls for plant B (P less than 0.001). In addition, the chromosome aberration frequency of smoking controls of plant A was significantly higher (P less than 0.01 when gaps excluded and P less than 0.05 when gaps included) than that of nonsmoking referents. Also, smokers among controls for plant B had an increased frequency of aberrations in their cultured blood lymphocytes when compared with nonsmokers. This difference was significant (P less than 0.05) when gaps were excluded.

Chromosome Aberrations↗
PubMed1984

Short-term bioassays of fractionated emission samples from wood combustion.

Extracts of an emission sample from wood burning, consisting of particles and volatiles, have been fractionated on an HPLC silica gel column into five fractions of increasing polarity. Nonfractionated samples and the individual fractions have been tested in three different short-term bioassays: the Ames Salmonella assay, the sister chromatid exchange (SCE) induction-test in Chinese hamster ovary cells (CHO), and the cell transformation test on Syrian hamster embryo (SHE) cells. Most of the total activity was found in the volatile part of the sample with all three bioassays, whereas the particle extract had the highest activity per unit mass extracted. The second most polar fraction contained most of the mass and was also highly active in all assays. The most polar fraction was very potent in the Salmonella assay, but showed only a weak response in the eukaryotic bioassays. Storage of the samples for several months at 0 degrees C revealed that the bacterial mutagens present in the most polar fraction were labile; the mutagenicity was almost totally lost after 1 year's storage.

Animals↗
PubMed1984

Erythrocyte-dependent metabolic activation of styrene and induction of sister chromatid exchange in cultured human lymphocytes.

Human erythrocytes can oxidize styrene to styrene-7,8-oxide in the absence of the co-factors required for metabolic reactions catalysed by the microsomal cytochrome P-450 system. This probably explains the increased incidence of sister chromatid exchanges (SCEs) that was detected in whole blood lymphocyte cultures from 11 male donors after treatment in vitro (48 h) with styrene (2 mM). Styrene-7,8-oxide (0.15 mM) also induced SCEs in these cultures. Styrene (0.5-4.0 mM) increased the incidence of SCEs only slightly in cultures of isolated lymphocytes (2 X 10(4) erythrocytes/ml), but had a clear dose-dependent effect in whole blood cultures (2-4 X 10(8) erythrocytes/ml). When erythrocytes were added to purified cultures, SCE incidence increased after treatment with styrene (2 mM). Cyclophosphamide elevated the incidence of SCEs almost equally efficiently in whole blood and in isolated lymphocytes. It is suggested that styrene induces SCEs after transformation to styrene-7,8-oxide by oxyhemoglobin in erythrocytes, whereas cyclophosphamide is activated by the lymphocytes themselves.

Biotransformation↗
PubMed1984

Detection of exposure to mutagenic compounds in low-tar and medium-tar cigarette smokers.

A volunteer study was carried out on groups smoking low-tar (5.4 mg/cig.) and medium-tar (16.3 mg/cig.) cigarettes and on non-smokers. The number of cigarettes smoked was recorded daily throughout a 51-day study period, and the effects of smoking were measured in the beginning and after 3-week terms of smoking medium-tar or low-tar cigarettes. The parameters measured were blood carboxyhemoglobin concentration, thioethers excreted into the urine, mutagenic activity in the urine, and the frequency of sister-chromatid exchanges in blood lymphocytes. For all four parameters, the differences between the smokers and the non-smokers were significant. However, within the study design no differences could be detected between low-tar or medium-tar cigarette smoking in the biological-monitoring tests used.

Adult↗
PubMed1984

Bacterial urinary assay in monitoring exposure to mutagens and carcinogens.

The bacterial bioassay procedure provides a sensitive test for the presence of mutagenic activity in urine. Its sensitivity for detecting the presence of individual chemicals may not be as high as that of specific analytical methods, but it has the following advantages: (1) many substances and metabolites may be active in a single assay, making it possible to detect mutagenic activity from unanticipated sources; (2) biological activity is demonstrated, rather than simply the presence of substances; or (3) the assay may also reflect the 'integrated' effect of multiple substances, although this capability has not been well characterized and (4) the assay can be easily coupled with a chemical analysis. The chief disadvantages of the test system are lack of sensitivity for certain specific substances, as compared to chemical techniques, and possible interference from substances normally present in urine (such as amino acids). The urinary mutagenicity assay is most useful when exposure to carcinogens and mutagens is suspected but when the specific chemical is unknown, when chemical analytical techniques are not available or when exposure is to undefined complex mixtures.

Antineoplastic Agents↗