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Biomedical subjects

H Norppa

Publications and source records attributed to H Norppa.

At least 91 records · Page 5Linked to original sources
PubMed1989

Induction of chromosome aberrations and sister-chromatid exchanges by caprolactam in vitro.

Caprolactam (CAP) induced chromosome aberrations in whole-blood cultures of human lymphocytes at 50 mM without metabolic activation (24-h treatment) and at 200 mM in the presence of rat liver S9 mix (1-h treatment). CAP also produced a dose-dependent increase in polyploid cells, the effect being statistically significant at 25 and 50 mM without S9 mix and at 100 and 200 mM with S9 mix. Without metabolic activation, there was an increase in hypodiploid cells at 50 mM and hyperdiploid cells at 12.5 mM. In Chinese hamster ovary cells, CAP produced a marginal elevation of sister-chromatid exchanges at 125 mM in the presence of S9 mix (4-h treatment). The results show that CAP is able to induce cytogenetic changes in vitro at very high toxic concentrations.

Adult↗
PubMed1988

Evaluation of sister chromatid exchange as an indicator of sensitivity to N-ethyl-N-nitrosourea-induced carcinogenesis in rats.

Sister chromatid exchange (SCE) frequencies in peripheral lymphocytes are a frequently used endpoint to indicate exposures to genotoxins in groups of humans. The aim of this study was to ascertain, in an experimental design, whether or not SCE rates have any association with the risk of cancer at the individual level in rats exposed to a known carcinogen. Individual SCE rates were determined in three consecutive analyses in cultured blood lymphocytes of 50 adult male Wistar rats. Analyses were done before as well as 24 hr and 7 days after a single intraperitoneal administration of 0, 25, 50, or 75 mg/kg of N-ethyl-N-nitrosourea (ENU). The animals were followed until death; also, the relationship between SCEs and carcinogenic outcome, i.e., the presence or absence of tumors, and their latency period were examined. ENU significantly decreased the life expectancy of the rats. The tumor types most clearly associated with ENU treatment were various gliomas and thyroid-gland and testicular tumors. ENU induced a moderate (maximally 1.6-fold) increase in the mean frequency of SCEs/cell at both sampling times after treatment. The effect was somewhat more pronounced 1 day rather than 1 week after treatment. The mean SCE rates in rats with ENU-specific cancers or in animals with early or multiple tumors did not differ from those in animals that survived no less than 65 weeks or longer without developing tumors. In ENU-treated animals with tumors, no relationship was found between the mean SCE rate and survival time. It is concluded that in outbred Wistar rats the SCE response in cultured lymphocytes does not indicate individual susceptibility to the carcinogenic action of ENU. On a group basis, however, animals with high SCE rates were shown to have increased risk of cancer.

Animals↗
PubMed1988

Single-strand breaks in DNA of peripheral lymphocytes of styrene-exposed workers.

Single-strand breaks (SSB) were determined by means of the DNA unwinding technique in peripheral lymphocytes of styrene-exposed workers and referents. A slight increase in SSB was observed among exposed subjects in comparison with a control group of office workers. A correlation was found between SSB, the excretion of mandelic acid and the concentration of styrene glycol in blood. The present work suggests that the DNA unwinding technique can be used for screening workers exposed to genotoxic compounds.

DNA Damage↗
PubMed1987

Induction of micronuclei by vinyl acetate in mouse bone marrow cells and cultured human lymphocytes.

A dose-dependent increase in micronucleated polychromatic erythrocytes was observed in the bone marrow of male C57B1/6 mice 30 h after a single intraperitoneal injection of vinyl acetate (250, 500, 1000 or 2000 mg/kg b.wt.; (9-14 animals per group). The effect was statistically significant at 1000 mg/kg (1.33 +/- 0.29% vs. 0.6 +/- 0.10% in olive oil-treated controls) and at 2000 mg/kg (1.57 +/- 0.19%) of vinyl acetate. These doses were fatal to 6 (1000 mg/kg) and 8 (2000 mg/kg) out of 14 animals in both groups. The ratio of polychromatic to normochromatic cells decreased as a function of vinyl acetate dose. Cyclophosphamide (20 mg/kg), used as a positive control chemical, induced a clear increase in micronucleated polychromatic erythrocytes (2.07 +/- 0.20%). None of the treatments affected the number of micronuclei in normochromatic erythrocytes. In human whole-blood lymphocyte cultures, micronucleus induction by a 48-h treatment with vinyl acetate (0.125, 0.25, 0.5, 1 and 2 mM; 24 h after culture initiation) was studied in lymphocytes with preserved cytoplasm from smear slides prepared by a method involving the removal of erythrocytes at harvest by sodium cyanide treatment to improve preparation quality. The frequency of micronucleated lymphocytes reached a peak at 0.5 mM (3.2 +/- 1.0% vs. 0.9 +/- 0.1% in control cultures) and 1 mM (3.1 +/- 0.7%), with a decline at 2 mM probably because of a toxic effect resulting in mitotic inhibition.

Animals↗
PubMed1987

Chromosome aberrations and sister-chromatid exchanges induced by technical grade toluene diisocyanate and methylenediphenyl diisocyanate in cultured human lymphocytes.

Technical-grade toluene diisocyanate (TDI; 80% 2,4-isomer and 20% 2,6-isomer) and 4,4'-methyl-enediphenyl diisocyanate (MDI; about 45% MDI, 25% 4,4'-methylenediphenyl triisocyanate and 30% unspecified compounds of higher molecular weight), used as hardeners in the production of polyurethane, induced chromosome aberrations after a 24 h treatment in the absence of metabolic activation in human whole-blood lymphocyte cultures, MDI at all doses tested (0.54-4.30 microliter/ml) and TDI (0.019-0.150 microliter/ml) at the highest two doses (0.075 and 0.150 microliter/ml). In the presence of rat liver S9 mix (1.5 h treatment), both mixtures significantly increased aberrations at only one of the doses used, MDI at the highest dose (4.30 microliter/ml) and TDI at the second highest dose (0.038 microliter/ml). MDI also marginally increased sister-chromatid exchanges at the highest dose available (2.17 microliter/ml) with and without (48 h treatment) S9 mix. On addition to culture medium, both TDI and MDI formed polymers, which were seen as small particles on the microscopic slides. At high doses the presence of these polymers made metaphase analysis impossible.

Animals↗
PubMed1985

Mutagenicity of selected organic solvents.

For certain organic solvents, such as benzene, vinyl chloride, styrene, technical grade trichloroethylene, and acrylonitrile, the available studies provide convincing evidence to demonstrate activity in short-term genetic assays. For a few solvents, such as phenol, vinyl toluene, ethanol, and tetrachloroethylene, the evidence is limited to a certain test system and/or test organism. For most of the solvents reviewed, studies are either lacking or they are so inadequate that no final evaluation on the mutagenic activity of the solvents can be made.

Animals↗
PubMed1985

Chromosome damage induced by vinyl acetate through in vitro formation of acetaldehyde in human lymphocytes and Chinese hamster ovary cells.

A 48-h treatment with vinyl acetate (0.05-1 mM) induced a drastic increase in sister chromatid exchanges (SCEs) and (in first division cells) structural chromosome aberrations in cultured human lymphocytes. The effects were more pronounced in cultures of isolated lymphocytes than in whole-blood cultures. A distinct dose-dependent induction of SCEs similarly occurred in Chinese hamster ovary cells after a 24-h vinyl acetate treatment (0.125-1 mM). A pulse treatment of Chinese hamster ovary cells for 4 h also yielded a clear increase in SCEs, but at higher concentrations (0.3-5 mM). The presence of rat liver S9 mix enhanced the SCE-inducing effect of vinyl acetate in Chinese hamster ovary cells. Gas chromatographic analysis of human whole-blood lymphocyte cultures treated for 10 s-20 min with vinyl acetate (5.4 mM) revealed a rapid degradation of vinyl acetate and formation of acetaldehyde. During the 20-min observation period, no degradation of vinyl acetate or formation of acetaldehyde were observed in complete culture medium without blood, which suggested that the reaction was enzymatic. Acetaldehyde induced SCEs in human whole-blood lymphocyte cultures at concentrations (0.125-2 mM) comparable to those used for vinyl acetate. The results indicate that vinyl acetate induces chromosome damage in cell cultures through enzyme-mediated hydrolysis to acetaldehyde.

Acetaldehyde↗
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↗
PubMed1983

Induction of sister-chromatid exchanges by styrene analogues in cultured human lymphocytes.

Styrene and 11 styrene analogues were tested for their ability to induce sister-chromatid exchanges (SCEs) by a 48-h treatment in human whole-blood lymphocyte cultures (72 h). Styrene, its methyl-substituted derivatives (substituted at 2-, 3-, 4-, 3,5- or beta-position) and two styrene oxides (3,5-dimethylstyrene-7,8-oxide and 4-nitrostyrene-7,8-oxide) induced a distinct dose-dependent increase in SCEs. Also, 4-methylstyrene-7,8-oxide and alpha-methylstyrene showed a positive effect, but were not able to double the mean number of SCEs/cell at the concentration ranges available. Ethylbenzene had a marginal effect on SCEs at the highest dose tested. 2-Phenylethanol did not increase SCEs. The results indicate that styrene and methylstyrenes are converted into reactive metabolites in the whole-blood lymphocyte cultures. The negative or weak effects of styrene analogues without a double bond in the side-chain (ethylbenzene and 2-phenylethanol) suggest that the reactive metabolites are derived from the conversion of the vinyl group and are styrene-7,8-oxides.

Cell Cycle↗
PubMed1983

Genetic toxicity of styrene and some of its derivatives.

Styrene, an important plastic monomer, is mutagenic after metabolic activation in several test systems. Probably because of an unfavorable activation : inactivation ratio, some mutagenicity assays have not, however, found styrene mutagenic. Styrene is converted by microsomal monooxygenases in vivo to styrene-7,8-oxide, which is a well-known mutagen. Arene oxides have also been proposed as the reactive metabolites of styrene, but the significance of these compounds is not yet fully understood. Only few derivatives of styrene have been tested for mutagenicity. The results are characterized by difficulties in metabolic activation. Many styrene-7,8-oxide analogues substituted at the phenyl ring are electrophilic reactants and mutagenic in vitro. Human whole-blood lymphocyte cultures have a peculiar feature, ie, styrene and many of its analogues substituted at the ring or vinyl chain induce sister chromatid exchanges in the cultured cells without exogenous metabolizing systems. This activation is brought about by erythrocytes present in the cultures and probably results from the conversion of styrenes to styrene-7,8-oxides.

Animals↗
PubMed1983

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↗