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Biomedical subjects

H Norppa

Publications and source records attributed to H Norppa.

At least 109 records · Page 6Linked to original sources
PubMed1981

Metabolism and genotoxicity of styrene.

An overview on the metabolism and genotoxicity of styrene is given in this article. The mutagenic potency of styrene has been confirmed in a number of test systems providing the metabolic activation of styrene. Styrene is converted to styrene-7,8-oxide as catalyzed by cytochrome P-450 cored enzyme complex. Styrene-7,8-oxide is mutagenic in prokaryotic and eukaryotic test systems without metabolic activation. It reacts with nucleic acid bases, especially with deoxyguanosine producing 7-alkylguanine and deoxycytidine producing N-3 alkylcytosine. Quite recently, styrene-7,8-oxide has been found to be a potent carcinogen in rats. In human whole blood cultures, styrene is metabolized into styrene-7,8-oxide. Styrene is able to induce both SCEs and chromosomal aberrations in cultured lymphocytes. The clastogenic action of styrene can be explained by the metabolism of styrene into styrene-7,8-oxide in cultured human blood cells. Although also an arene oxide, styrene-3,4-oxide, has been suggested in the biotransformation of styrene, the evidence so far supports the view that the vinyl group oxidation and oxirane formation plays a predominant role in the genotoxicity of styrene.

Animals↗
PubMed1981

The in vitro induction of sister chromatid exchanges and chromosome aberrations in human lymphocytes by styrene derivatives.

Three structural analogues of styrene, vinyltoluene (40% para-, 60% meta -isomers), 4-methoxy-trans-beta-chlorostyrene and trans-beta-nitrostyrene, were tested for their potential to induce chromosome aberrations and sister chromatid exchanged (SCE) in phytohaemagglutinin-stimulated human lymphocytes cultured for 48 h (aberration analysis) or 72 h (SCE analysis). The treatments were carried out 24 h (aberrations) or 48 h (SCEs) before harvest. The toxicity of vinyltoluene to cultured lymphocytes was similar to that of styrene while 4-methoxy-beta-chlorostyrene was about 10 times and beta nitrostyrene about 100 times more toxic than styrene. A dose-dependent increase of SCEs and chromosome aberrations was observed in cells treated with vinyltoluene (0.33-4.00 mM) or with 4-methoxy-beta-chlorostyrene (0.5-1.00 mM). No effect could be seen in cultures treated with beta-nitrostyrene (0.004-0.044 mM). The results suggest that, like styrene, vinyltoluene and 4-methoxy-beta-chlorostyrene also are converted in vitro in reactive metabolites, presumably epoxides.

Cells, Cultured↗
PubMed1981

Monitoring genotoxicity in the occupational environment.

New methods need to be developed for the biological monitoring and health surveillance of workers occupationally exposed to mutagenic and carcinogenic chemicals. Two potential approaches, the assay of urine for mutagenicity and the analysis of chromosomal changes in lymphocytes of workers, are discussed in this report with respect to experience in two occupational environments, the rubber industry and a hospital oncology unit. The urine of workers in the rubber industry has shown significantly increased mutagenic activity after the workweek in comparison to postvacation values. Handling cancer chemotherapeutic drugs in oncology units may cause exposure to the cytostatics, many of which are known mutagens and carcinogens. This exposure can be detected as an increased sister chromatid exchange frequency in cultured lymphocytes.

Antibiotics, Antineoplastic↗
PubMed1980

Chromosomal aberrations in bone marrow of Chinese hamsters exposed to styrene and ethanol.

No significant increase was detected in the number of chromosomally damaged cells in bone marrow of Chinese hamsters after either inhalation exposure to 300 ppm styrene or oral intake of 15% ethanol in drinking water (exposure time 4 days or 3 weeks). In combined exposure, a slight increase of chromosomal aberrations was observed in the group exposed for 4 days (2.0% aberrant cells vs. 0.0% in controls). The group exposed for 3 weeks to combined treatment showed no response (0.3% aberrant cells vs. 0.7% in controls).

Animals↗
PubMed1980

Styrene and styrene oxide induce SCEs and are metabolised in human lymphocyte cultures.

Both styrene and its presumed active metabolite styrene oxide show dose response as potent inducers of sister chromatid exchanges (SCEs) in human lymphocyte cultures. The SCE inducing and clastogenic capacity of styrene in lymphocytes in vitro can be explained by gas chromatographically measurable increase of styrene oxide in styrene treated cultures.

Biotransformation↗
PubMed1980

Increased sister chromatid exchange frequencies in lymphocytes of nurses handling cytostatic drugs.

In oncology units, personnel handling chemotherapeutic drugs may occasionally be exposed to small amounts of genotoxic agents. This exposure was obviously the cause of the increased frequencies of sister chromatid exchange (SCE) observed in nurses in daily contact with cytostatics (N = 20, mean SCEs/cell +/- SE 9.4 +/- 0.3) as compared to a group of office workers (N = 10, mean SCEs/cell 8.1 +/- 0.3). The oncology nurses also had a higher SCE frequency than other hospital nurses (N = 10, mean SCEs/cell 8.7 +/- 0.2), but this difference was not statistically significant. The SCEs of patients under chemotherapy were about five times higher (mean SCEs/cell 36.8 +/- 0.6) than those of healthy subjects.

Antineoplastic Agents↗
PubMed1979

Effects of styrene oxide on chromosome aberrations, sister chromatid exchange and hepatic drug biotransformation in chinese hamsters in vivo.

In vivo inhalation exposure to styrene oxide (25, 50, 75 and 100 ppm) for 2, 4 or 20 days (25 ppm only) had no effects on chromosomal aberration rates or sister chromatid exchange (SCE) frequencies (BrdU/labelling performed in vitro) in the bone marrow cells of Chinese hamsters. The only positive response in aberration frequency was obtained when styrene oxide was injected in lethal concentration (500 mg/kg body weight, i.p.) into the animal. One animal out of six showed slightly elevated SCE values after this high dose. The response of the hepatic drug metabolizing enzymes to styrene oxide exposure was found to be rather weak, which may be due to rather high activity of epoxide hydratase in Chinese hamsters as compared to e.g. mouse.

Animals↗
PubMedDate not supplied

Induction of chromosome aberrations by styrene and vinylacetate in cultured human lymphocytes: dependence on erythrocytes.

Two vinyl monomers, styrene and vinylacetate, were tested for their ability to induce chromosome aberrations in cultured human lymphocytes. The effects of a 24-h treatment (48 h after culture initiation) were studied both in whole-blood cultures (with 2 X 10(8) erythrocytes/ml) and in isolated lymphocytes (with 4000 erythrocytes/ml). Styrene produced a clear dose-dependent increase in chromatid-type aberrations in whole-blood cultures (0.5-6 mM) and a weaker effect in cultures of isolated lymphocytes (1-4 mM). A statistically significant elevation in aberrations was observed at 2 mM in the former culture type and at 1 mM in the latter. These results support earlier studies on the importance of erythrocytes in the metabolic activation of styrene, but also suggest that a part of this activation occurs in the lymphocytes themselves. Vinylacetate (0.125-2 mM), the more potent clastogen of the two monomers tested, induced a distinct dose-dependent increase in chromatid-type aberrations and a slight elevation in chromosome-type breaks in both culture types. The lowest concentration giving a positive result was 0.25 mM. The clastogenic effects of vinylacetate were somewhat more pronounced in isolated lymphocytes than in whole blood. Vinylacetate is known to be rapidly hydrolyzed in vitro to acetaldehyde, which probably explains the positive result.

Biotransformation↗
PubMedDate not supplied

Sister-chromatid exchanges in lymphocytes of smokers in an experimental study.

The frequency of sister-chromatid exchanges (SCEs) was studied in peripheral blood lymphocytes of 26 young male smokers and 10 non-smokers who had recently entered military service. The levels of SCEs were examined in 4 consecutive blood samples taken after short experimental periods of smoking only low-tar (LT) or medium-tar (MT) cigarettes. The incidence of SCEs was significantly higher in the the group of smokers than in the group of non-smokers. The SCE levels of the smokers were found to be associated with the personal smoking history; the observed increase in the SCE frequency correlated with the years of smoking measured as cumulative pack years. The difference in type of cigarette did not influence the SCE frequencies.

Adolescent↗
PubMedDate not supplied

Styrene and vinyltoluene induce micronuclei in mouse bone marrow.

Male C57BL/6 mice were treated i.p. with a single dose of styrene (250, 500, 1000 or 1500 mg/kg b.wt; 4 animals/group), vinyltoluene (100, 200, 300 or 500 mg/kg b.wt; 4-5 animals/group) or olive oil (controls, 13 animals). A significant increase in micronucleated polychromatic erythrocytes was observed at 250 and 1000 mg/kg b.wt of styrene and at 200, 300 and 500 mg/kg b.wt of vinyltoluene. 1000 and 1500 mg/kg b.wt of styrene and 100, 200 and 300 mg/kg b.wt of vinyltoluene significantly decreased the ratio of polychromatic to normochromatic erythrocytes. There was no increase in normochromatic cells with micronuclei.

Animals↗