Search PubMed⌕ Search

Biomedical subjects

H Vainio

Publications and source records attributed to H Vainio.

At least 307 records · Page 17Linked to original sources

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↗

Effects of methylene chloride, trichloroethane, trichloroethylene, tetrachloroethylene and toluene on the development of chick embryos.

Toluene and 5 aliphatic chlorinated hydrocarbons of wide industrial use were injected into the air space of fertilized chicken eggs at 2, 3 and 6 days of incubation. The embryotoxicity was evaluated as survival and death incidences after 14 days of incubation, and also the weights and lengths of the embryos were recorded. The approximate LD50 value for trichloroethylene and trichloroethanes varied between 50 and 100 mumol/egg while for toluene, tetrachloroethylene and methylene chloride it was over 100 mumol/egg. Macroscopic malformations of various kinds were produced with doses of 5-100 mumol/egg. The teratogenic potential of the tested compounds decreased in the following order: 1,1,1-trichloroethane greater than trichloroethylene greater than methylene chloride, tetrachloroethylene, 1,1,2-trichloroethane greater than toluene greater than olive oil control.

Abnormalities, Drug-Induced↗

Carbon disulphide induced activation of liver UDP glucuronosyltransferase in rats pretreated with phenobarbitone.

Carbon disulphide (CS2) exposure has been shown to activate the UDP glucuronosyltransferase of liver microsomes in rats pretreated with phenobarbitone. Now the nature of CS2 induced activation of the enzymes has been studied further. Phenobarbitone pretreated rats were exposed to 0.15% CS2 for 2 hrs on two successive days. The activity of UDP glucuronosyltransferase was measured from the liver microsomes after the enzymes was activated by incubation of the microsomes with various concentrations of the detergents Triton X-100, digitonin and cetylpyridinium chloride. The exposed animals showed an increased enzyme activity at all applied concentrations of the detergents; therefore in addition to membrane destruction by CS2 exposure, some other mechanism must also be involved in the CS2 induced activation of liver microsomal UDP glucuronosyltransferase. The changes in membrane lipid-protein interactions with l-anilino-8-naphthalene sulphonate (ANS) were also probed. The CS2 exposed animals had more high-affinity binding sites for ANS in their liver microsomal membranes, and in addition the quantum yield of ANS fluorescence was enhanced by CS2. The changes differed from those found after carbon tetrachloride exposure and suggest that, even if the two drugs have some common effects on microsomes, e.g. UDP glucuronosyltransferase activation, P-450 destruction and lipid peroxidation induction, the changes they cause in the microsomal micro-environment differ.

Animals↗

Embryotoxicity and teratogenicity of styrene and styrene oxide on chick embryos enhanced by trichloropropylene oxide.

The effects of TCPO (trichloropropylene oxide) on the embryotoxicity and teratogenicity of styrene and styrene oxide and chick embryos were investigated. The compounds were injected into the air space of the eggs in a total volume of 25 microliter on the third day of embryogenesis. TCPO increased embryotoxicity and teratogenicity of styrene and styrene oxide. Our results present evidence that the epoxides possess embryotoxic and teratogenic properties in chick embryos.

Abnormalities, Drug-Induced↗

Styrene and styrene oxide concentrations in the air during the lamination process in the reinforced plastics industry.

Styrene and styrene oxide concentrations were measured during the lamination process in the reinforced plastics industry. The mean concentration of styrene in the personal samples was 130 ppm, the highest value measured being 350 ppm. The average concentration for styrene oxide alone was 0.1 ppm, whereas the corresponding measurement for styrene oxide and its decomposition products combined was 0.7 ppm. In comparison then, the concentrations of styrene oxide and its derivatives were much lower (about 0.5% of the total) than those of styrene.

Air↗

Glucuronidation of 3-hydroxybenzo(a)pyrene in liver microsomes.

A simple and sensitive fluorimetric method is described for evaluation of 3-hydroxybenzo(a)pyrene conjugation with UDPglucuronic acid. It is less expensive than a radiochemical method and suitable for routine use. 3-Hydroxybenzo(a)pyrene is readily conjugated in isolated liver microsomes in the presence of UDPglucuronic acid. Activity in rat liver microsomes was 0.90--1.20 nmol.min-1.mg-1 microsomal protein. The activity in homozygous and heteroxygous Gunn rats was considerably lower than in Wistar rats. Activity in guinea pigs was 2.5--3 nmol.min-1.mg-1 protein. 3-Methylcholanthrene pretreatment (20 mg/kg of body weight for 4 consecutive days) of rats enhanced the hepatic UDPglucuronosyltransferase activity 2--5 fold. In untreated microsomal membranes of rat liver the apparent Km for 3-hydroxybenzo(a)pyrene was 0.09 mM and for Udpglucuronic acid 4.6 mM. Conjugation with UDPglucose did not occur. 4-Nitrophenol and 4-nitrophenyl-beta-D-glucuronide behaved like non competitive inhibitors. In contrast to 4-nitrophenol conjugation, both ionic (cholic acid) and non-ionic (Triton X-100, digitonin) surfactants had no effect or inhibited the glucuronic acid conjugation of 3-hydroxybenzo(a)pyrene in rat liver microsomes as also did the treatment of microsomal membranes with phospholipases A and C. Trypsin was almost without an effect on UDPglucuronosyltransferase activity when 3-hydroxybenzo(a)pyrene was used as substrate.

Animals↗

Effects of intermittent styrene inhalation, ethanol intake and their combination on drug biotransformation in rat liver and kidneys.

The modifying effects of daily ethanol ingestion in the drinking water as a 15 % solution (v/v) on drug biotransformational changes induced by inhalation exposure to styrene (300 ppm or 1260 mg/m3, 6 h daily, 5 d/week, up to 17 weeks) were studied in rat liver and kidney. The drug hydroxylation activities (7-ethoxycoumarin O-deethylase and 2,5-diphenyloxazole hydroxylase) both in liver and in kidneys were increased more by ethanol ingestion than by styrene inhalation. When administered in combination, styrene and ethanol exerted mostly an additive enhancing effect. However, hepatic NADPH-cytochrome c reductase activity was reduced both in styrene and in ethanol-treated rats. Hepatic styrene oxide hydratase activity was virtually unaffected by styrene treatments. The depression of glutathione concentration in liver was greater after styrene-ethanol than after styrene treatment alone. The hepatic UDPglucuronosyltransferase activity was enhanced slightly both in styrene and in styrene-ethanol rats. The binding affinity of styrene towards cytochrome P-450 was increased after styrene inhalation as shown by lowered K8 values. The perirenal fat concentration of styrene showed a rough inverse relationship to the overall monooxygenation activities in liver and kidney. Despite the additively induced enzyme activities in styrene-ethanol-treated rats the accumulation of styrene in fat of these animals was on the whole somewhat greater, suggesting that these two solvents in vivo also have mutual inhibitory effects on biotransformation.

Animals↗

Biochemical and toxicological effects of short-term, intermittent xylene inhalation exposure and combined ethanol intake.

Intermittent inhalation of 300 ppm of xylene vapour 6 h daily for 2 weeks caused a marked accumulation of the solvent in the perirenal fat. Simultaneous ethanol ingestion reduced the solvent load significantly although the perirenal xylene concentration increased in both test groups between the first and second week of exposure. Xylene inhalation enhanced hepatic and renal ethoxycoumarin 0-deethylase activity about 1.5-fold. The combination of inhaled xylene and peroral ethanol showed a markedly potentiated effect on microsomal ethoxycoumarin 0-deethylase activity especially in the kidneys. The enhanced monooxygenase activity was compatible with the decreased body solvent burden. Therefore, simultaneous ethanol intake might significantly modify the toxicological hazard in xylene exposure. Slightly increased proteolysis was detected in brain of animals in the xylene-ethanol experiment after the second week. Brain RNA content decreased after 2 weeks of exposure in the ethanol consuming animals. Xylene inhalation enhanced cerebral DT-diaphorase activity in both groups after 2 weeks of exposure. Ethanol intake also potentiated the behavioural effects caused by the solvent inhalation.

Animals↗

Vinyl chloride and vinyl benzene (styrene)--metabolism, mutagenicity and carcinogenicity.

Vinyl chloride and vinyl benzene (styrene) are mutagenic in microbial tests, in Drosophila, in yeast, and in mammalian cells. Reports from various countries have shown an excess of chromosomal aberrations in the lymphocytes of workers exposed to vinyl chloride monomer when the workers were compared with controls. Workers occupationally exposed to styrene also revealed a clear increase in the rate of chromosome aberrations in their lymphocytes. Both chloroethylene oxide and styrene oxide, the primary biotransformation products of vinyl chloirde and styrene respectively, bind covalently to cellular macromolecules. Vinyl chloride is a carcinogen in both animals and man. Styrene is currently being tested in animals. These findings, the demonstration of mutagenic response via microbial and other test systems and with observations of significant excesses of chromosomal aberrations among workers exposed to these agents, raise scientific and health oriented concern about the possible genetic risks of vinyl chloride and styrene to man.

Animals↗

Cytogenetic effects of styrene and styrene oxide.

Styrene and styrene oxide induce various cytogenetic effects, similar in both human lymphocytes in vitro and onion root-tip cells in vivo. Styrene appears to cause chromosome breakage in both systems, and in Allium it shows a strong c-mitotic effect. Styrene oxide, on the other hand, seems to destroy the tertiary folding of the chromatin. Cytotoxicity of styrene oxide is very high (complete mitotic inhibition occurs on 0.03% v/v) in human lymphocytes, whereas, in Allium, styrene is slightly more toxic than styrene oxide. Styrene glycol, a further metabolite of styrene oxide, does not cause mitotic inhibition.

Cells, Cultured↗

Urinary thioether of employees of a chemical plant.

The thiols in the morning urine of 224 employees of a chemical plant were determined after alkaline hydrolysis of all urinary thioethers. The highest thioether excretion was found in rubber workers and radial tyre builders in comparison with clerks, plastic monomer mixers and footwear preparers. Smoking and medication tended to increase thioether excretion. Urinary thioether determination may prove to be a valuable tool in assessing exposure to mixtures of chemicals regardless of the route of absorption.

Acetylcysteine↗

Biochemical and toxicological effects of combined exposure to 1,1,1-trichloroethane and trichloroethylene on rat liver and brain.

1. Inhalation exposure of adult male rats to a mixture of 1,1,1-trichloroethane (500 p.p.m.) and trichloroethylene (200 p.p.m.) for four days 6 h daily resulted in an accumulation of 1,1,1-trichloroethane in perirenal fat. Further exposure on the fifth day caused a rapid increase in various organ contents of both solvents with secondary depression of brain RNA. 2. The four-day exposure doubled the RNA content of liver and caused a slight decline in the concentrations of glutathione in liver. 3. The amount of cytochrome P-450 in liver was increased, as well as the overall mono-oxygenase activity, measured with styrene as substrate. During continuing treatment on the fifth day, styrene mono-oxygenase activity decreased, the activity after 6 h being only about 50% of that at the beginning of the fifth day of exposure. 4. UDP-glucuronosyl transferase activity (measured in digitonin-activated microsomes) was doubled by the four-day combined exposure to 1,1,1-trichloroethane and trichloroethylene. 5. The changes during the fifth day of exposure, e.g. rapid increase in the concentrations of solvents in organs, the detection of trichloroethylene in tissues and depression of mono-oxygenase activity, obviously also occurred during the exposures on days 1 to 4 and reverted during each post-exposure period.

Animals↗

Cytogenetic effects of styrene and styrene oxide on human lymphocytes and Allium cepa.

Styrene and styrene oxide induce cytogenetic effects already at very low concentrations (0.01% v/v or even less); the effects are similar in both in vitro human lymphocytes and in vivo onion root tip cells (Allium cepa L.). It is characteristic that styrene treatment is more potent in causing chromosome breakage in both systems. In Allium styrene induced inhibition of mitotic spindle action as revealed by a strong c-mitotic effect. Also the number of micronuclei and nuclear bridges increased in both test systems, especially after styrene oxide treatment. Furthermore, the metaphase chromosome morphology in the cells treated with styrene oxide was strongly affected. In both systems, chromosome destruction was observed, or else the chromosome material was decondensed and resulted in a characteristic fuzzy appearance of Allium chromosomes or a banded appearance of human lymphocyte chromosomes. A specific effect of styrene oxide on the chromosomal proteins is thus suggested. The data obtained from the autoradiographic studies with Allium support the idea that [7--3H] styrene oxide binds irreversibly to the cytoplasmic and nuclear macromolecules.

Autoradiography↗

Thermal degradation products of homopolymer polystyrene in air.

Polystyrene without additional compounds was treated in a laboratory oven at elevated temperatures (200 degrees, 350 degrees, 500 degrees C) under slight air flow (0.7 l/min). The thermal degradation products appearing in different phases (gases, vapors, aerosols) were collected and analyzed by methods of chromatography. Thermogravimetric analysis showed the thermal degradation of the polymer to begin at 270 degrees C in air and stop at 425 degrees C. The main groups of vaporized compounds generated were monoalkyl-substituted aromatic hydrocarbons and their oxidized products, of which styrene monomer and benzaldehyde were the most abundant. Only trace amounts of carbon monoxide and aliphatic compounds (hydrocarbons, aldehydes, and acids) were produced. The aerosol produced, the amount of which increased as the temperature rose, contained mainly fragments of the polymer chain (e.g., dimers and trimers of styrene). The traces of styrene, cumene, and ethylbenzene that appeared at 200 degrees could represent residual compounds in the initial polymer and indicate the beginning of the thermal degradation. If proportional concentrations are kept as a criterion, the important products, from the point of view of industrial hygiene, were styrene, benzaldehyde, styrene oxide, acetophenone, and l-phenylethanol. The large amount of aerosol that appeared may also be of practical importance.

Acids↗

Chromosome aberrations in lymphocytes of workers exposed to styrene.

Workers exposed to styrene in the reinforced plastics industry show a significant increase of chromosome aberrations, mainly chromosome breaks, in peripheral blood lymphocytes. The high incidence of aberrant lymphocytes (mean 15.1 +/- 4.8%; referents 2.0 +/- 1.3 %) was retained when the same men were reexamined one year later (mean 16.2 +/- 2.9 %). However, the frequency of sister chromatid exchanges (SCE), a newly developed sensitive parameter for the detection of recombinational exchanges linked with DNA repair, was not significantly increased (mean 5.3 +/- 1.0 SCE/cell) in comparison to the referents (mean 4.4 +/- 0.6 SCE/cell). This finding suggests a specific role of styrene or its metabolites in inducing genetic lesions mainly manifesting themselves as chromosomal breaks.

Adult↗