| 1. |
- Jarvis, Ian W H, et al.
(författare)
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Interactions between polycyclic aromatic hydrocarbons in complex mixtures and implications for cancer risk assessment
- 2014
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Ingår i: Toxicology. - Stockholm : Karolinska Institutet, Institute of Environmental Medicine. - 0300-483X .- 1879-3185.
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Tidskriftsartikel (refereegranskat)abstract
- In this review we discuss the effects of exposure to complex PAH mixtures in vitro and in vivo on mechanisms related to carcinogenesis. Of particular concern regarding exposure to complex PAH mixtures is how interactions between different constituents can affect the carcinogenic response and how these might be included in risk assessment. Overall the findings suggest that the responses resulting from exposure to complex PAH mixtures is varied and complicated. More- and less-than additive effects on bioactivation and DNA damage formation have been observed depending on the various mixtures studied, and equally dependent on the different test systems that are used. Furthermore, the findings show that the commonly used biological end-point of DNA damage formation is insufficient for studying mixture effects. At present the assessment of the risk of exposure to complex PAH mixtures involves comparison to individual compounds using either a surrogate or a component-based potency approach. We discuss how future risk assessment strategies for complex PAH mixtures should be based around whole mixture assessment in order to account for interaction effects. Inherent to this is the need to incorporate different experimental approaches using robust and sensitive biological endpoints. Furthermore, the emphasis on future research should be placed on studying real life mixtures that better represent the complex PAH mixtures that humans are exposed to.
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| 2. |
- Gunnarsson, David, et al.
(författare)
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Cadmium-induced decrement of the LH receptor expression and cAMP levels in the testis of rats
- 2003
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Ingår i: Toxicology. - 0300-483X .- 1879-3185. ; 183:(1-3), s. 57-63
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Tidskriftsartikel (refereegranskat)abstract
- Cadmium (Cd) is a widespread environmental pollutant, characterized by its ability to affect various organs. Adverse effect of Cd on the testis including decreased testosterone production are well-known phenomena, but the cellular events explaining these effects have not yet been established. In the present study the initial steps of gonadotropin mediated testosterone biosynthesis were examined in vivo in rats, in relation to Cd dose and time after injection. In the dose–response experiment Male Sprague–Dawley rats received a single subcutaneous (sc) injection of CdCl2 (1, 5 or 10 μmol/kg body weight) and were sacrificed 48 h after injection. A statistically significant decrease in luteinizing hormone (LH) receptor mRNA level in the testicular tissue was demonstrated at the highest dose (10 μmol/kg). In the temporal–response experiment rats were given 10 μmol/kg of CdCl2 sc and sacrificed 0.48, 4.8, 48 or 144 h after injection. LH receptor mRNA levels as well as cyclic adenosine monophosphate (cAMP) levels were found to be significantly lowered at 48 and 144 h. These observations of the mechanisms whereby Cd exerts its effect on the initial steps of testosterone biosynthesis are the first from in vivo experiments.
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| 3. |
- Hultberg, Björn, et al.
(författare)
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Interaction of metals and thiols in cell damage and glutathione distribution: potentiation of mercury toxicity by dithiothreitol
- 2001
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Ingår i: Toxicology. - 0300-483X. ; 156:2-3, s. 93-100
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, we have investigated the effects of extracellular redox status and metal/thiol interactions on glutathione distribution in HeLa cell cultures. No effects were seen on glutathione distribution after the addition of different thiols, whereas the pro-oxidant copper ions affected glutathione distribution in several ways. The addition of dithiothreitol (DTT) but not the other thiols potentiated the effects of mercury ions on glutathione distribution and cell toxicity. In the presence of DTT, increased intra- and extracellular glutathione concentrations were noted already at 0.05 micromol/l, which was below the previously reported toxicity threshold for mercury ions in blood. Likewise DTT potentiated the effects of copper ions on glutathione distribution and cell toxicity, whereas the addition of DTT to cell cultures with a non-metal thiol reactive agent (hydroquinone) or an oxidative agent (hydrogen peroxide) did not affect glutathione distribution or cell toxicity. Thus, it seems as the synergistic effects between DTT and thiol reactive agents only apply to metal ions.
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| 4. |
- Hultberg, Björn, et al.
(författare)
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Lipoic acid increases glutathione production and enhances the effect of mercury in human cell lines.
- 2002
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Ingår i: Toxicology. - 0300-483X. ; 175:1-3, s. 103-110
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Tidskriftsartikel (refereegranskat)abstract
- Thiols are known to influence the metabolism of glutathione. In a previous study (Toxicology 156 (2001) 93) dithiothreitol (DTT) did not show any effect on intra- or extracellular glutathione concentrations in HeLa cell cultures but increased the effects of mercury ions on glutathione concentrations, whereas monothiols such as N-acetylcysteine (NAC) or glutathione did not. In the present study, we have investigated the effects of thiols as well as the interaction between thiols and mercury ions in cultures of both HeLa and hepatoma cells. Furthermore, we have added alpha-lipoic acid (LA) to the previously used test panel of thiols, since it is metabolised intracellularly to a dithiol (dihydrolipoate). The present study shows that LA increased intra- and extracellular concentrations of glutathione in both HeLa and hepatoma cell cultures. In contrast to results for HeLa cells, the presence of DTT increased the intracellular glutathione concentration in hepatoma cells. No increase of glutathione concentrations was observed in hepatoma cell cultures in the presence of the monothiols (NAC, homocysteine or glutathione) tested, in agreement with previous findings in HeLa cell cultures. The presence of dithiols, either DTT or dihydrolipoate (the metabolite of LA), increased the effects of mercury ions on glutathione concentrations in hepatoma cells, whereas monothiols such as NAC or glutathione did not, in agreement with previous findings in HeLa cells. Thus, metabolic effects of mercury ions were observed in hepatoma cells as well as in HeLa cells at a lower concentration than the supposed toxicity threshold for mercury in blood.
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| 5. |
- Kjellstrand, Per, et al.
(författare)
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Effects of organic solvents on motor activity in mice
- 1985
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Ingår i: Toxicology. - 0300-483X. ; 35:1, s. 35-46
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Tidskriftsartikel (refereegranskat)abstract
- Groups of male mice were exposed via inhalation to methylene chloride, perchloroethylene, toluene, trichloroethylene or 1,1,1-trichloroethane. The exposures were started at 2300 h. Generation of vapor was stopped after 1 h. Motor activity of the animals during the exposures was measured with a Doppler radar. Several concentrations of each solvent were tested. Concentrations could be found for all solvents at which they initially increased the motor activity. When the generation of vapor was terminated and the concentration started to decline, a new phase of changes in motor activity was induced. At this phase, motor activity was in most cases influence in the opposite direction to that at the beginning of the exposure. Trichloroethylene concentrations could be found which gave no increase in activity at the start of exposure but a prominent decrease at termination. The lowest concentration at which effects could be seen was different for the different solvents. Perchloroethylene was more and 1,1,1-trichloroethane less potent than the other solvents in inducing motor activity. The time pattern of the motor activity alterations was specific for each solvent. Both the concentration and the rate of the concentration increase were responsible for the effects on motor activity. The differences between the solvents probably reflect differences in their site of action, their distribution and their biotransformation.
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| 6. |
- Kjellstrand, Per, et al.
(författare)
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Trichloroethylene: Effects on body and organ weights in mice, rats and gerbils
- 1981
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Ingår i: Toxicology. - 0300-483X. ; 21:2, s. 105-115
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Tidskriftsartikel (refereegranskat)abstract
- The influence of continuous inhalation of 150 ppm trichloroethylene (TCE) on body, liver, spleen, and kidney weights in rats, mice, and mongolian gerbils was tested. An age dependent decrease in body weight gain was observed in female rats exposed to TCE. All 3 spcies showed liver enlargement caused by the exposure. The effect was much more pronounced in mice, in which the increase was 60–80%, than in rats and gerbils where it was only 20–30%. After the end of the TCE-exposure the liver weights of the mice decreased rapidly. After 5 days of rehabilitation to the weight was only 10–20% higher than that of the controls. This difference persisted for at least 25 days. The spleen weight appeared unaffected or somewhat smaller in TCE-exposed animals of all species. An increased kidney weight (15%) was observed in TCE-exposed gerbils. This effect was less pronounced in mice and rats. Effects on the liver have earlier been seen only after exposure to concentrations much higher than that used in the present study. This difference is results in proposed to be due to the different schedules used for the exposure.
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| 7. |
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| 8. |
- Lindh, Christian, et al.
(författare)
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Binding of the potent allergen hexahydrophthalic anhydride in the mucosa of the upper respiratory and alimentary tract following single inhalation exposures in guinea pigs and rats
- 1999
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Ingår i: Toxicology. - 0300-483X. ; 134:2-3, s. 153-168
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Tidskriftsartikel (refereegranskat)abstract
- Hexahydrophthalic anhydride (HHPA; CAS No. 13149-00-3) is a highly allergenic compound commonly used in the chemical industry. Guinea pigs and rats were exposed to [3H2]HHPA by inhalation for 3-8 h and were killed at various intervals during 7 days. The tissue distribution of non-volatile and covalently bound radioactivity was studied by autoradiography. Tissue bound radioactivity was mainly found in the mucosa of the upper respiratory airways, whereas negligible levels were observed in the lungs. In addition, tissue bound radioactivity was present in the gastrointestinal tract and conjunctiva. Moreover, in the cortex of the kidneys in rats, but not in guinea pigs, a low level of tissue bound radioactivity was found. The radioactivity in the tissues persisted for at least 7 days after the end of exposure. Plasma proteins and soluble proteins from trachea, lung, and kidney from [3H2]HHPA-exposed animals were separated by gel filtration. The radioactivity in dialysed plasma was mainly found in the same fractions as albumin. The soluble proteins from trachea, lung, and kidney in both rats and guinea pigs showed a similar pattern as found in blood. The radioactivity in dialysed plasma from both guinea pigs and rats seemed to decay according to a two-compartment model. The non-extractable binding of [3H2]HHPA in the upper respiratory airways and conjunctiva may be of relevance for symptoms in workers with allergy, since they mainly develop symptoms and signs from the nose and eyes.
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