| 1. |
- Jarvis, Ian W H, et al.
(author)
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Nanomolar levels of PAHs in extracts from urban air induce MAPK signaling in HepG2 cells
- 2014
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In: Toxicology Letters. - Stockholm : Karolinska Institutet, Institute of Environmental Medicine. - 0378-4274 .- 1879-3169.
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Journal article (peer-reviewed)abstract
- Polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants that occur naturally in complex mixtures. Many of the adverse health effects of PAHs including cancer are linked to the activation of intracellular stress response signaling. This study has investigated intracellular MAPK signaling in response to PAHs in extracts from urban air collected in Stockholm, Sweden and Limeira, Brazil, in comparison to BP in HepG2 cells. Nanomolar concentrations of PAHs in the extracts induced activation of MEK4 signaling with down-stream increased gene expression of several important stress response mediators. Involvement of the MEK4/JNK pathway was confirmed using siRNA and an inhibitor of JNK signaling resulting in significantly reduced MAPK signaling transactivated by the AP-1 transcription factors ATF2 and c-Jun. ATF2 was also identified as a sensitive stress responsive protein with activation observed at extract concentrations equivalent to 0.1 nM BP. We show that exposure to low levels of environmental PAH mixtures more strongly activates these signaling pathways compared to BP alone suggesting effects due to interactions. Taken together, this is the first study showing the involvement of MEK4/JNK/AP-1 pathway in regulating the intracellular stress response after exposure to nanomolar levels of PAHs in environmental.
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| 2. |
- Barany, E, et al.
(author)
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Relationships between trace element concentrations in human blood and serum
- 2002
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In: Toxicology Letters. - 1879-3169 .- 0378-4274. ; 134:1-3, s. 177-184
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Journal article (peer-reviewed)abstract
- Trace element interactions can affect the absorption, metabolism, or effects of elements. Also, different elements may derive from the same source. Associations in biological media between element concentrations may indicate such phenomena. A large number of correlations were found between 13 trace elements (Co, Cu, Zn, Se, Rb, Rh, Pd, Cd, W, Pt, Hg, Tl, and Pb) in human blood and/or serum, as investigated in 372 Swedish adolescents. Notably, serum Se correlated with blood Ph and blood Hg and Cu and Zn were correlated to each other in both blood and serum. The elements Pt, Pd and Rh, spread in the environment through use of catalytic converters in cars, were closely correlated in both blood and serum. Apart from the correlations with a probable biological or exposure-related explanation, several other correlations, of yet unknown importance and origin, were found.
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| 3. |
- Kjellstrand, Per, et al.
(author)
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Effects of Trichloroethylene inhalation on acid phosphatase in rodent brain
- 1982
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In: Toxicology Letters. - : Elsevier BV. - 1879-3169 .- 0378-4274. ; 10:1, s. 1-5
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Journal article (peer-reviewed)abstract
- Rats, mice and gerbils were continuously exposed to 150 ppm trichloroethylene (TCE) for 30 days. In all three species, there was a marked increase in liver weight. In mice the weight increased more (86%) than in rats and gerbils (20%). After exposure the activity of acid phosphatase, a lysosomal marker enzyme, was tested in different brain areas, using a system which had a limit of detection of ± 10–15%. In most areas no significant influence was found. However, in the brain stem of mice and gerbils the phosphatase activity increased by approx. 10%.
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| 4. |
- Kjellstrand, Per, et al.
(author)
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Pitfalls in the interpretation of long-term inhalation experiments
- 1984
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In: Toxicology Letters. - : Elsevier BV. - 1879-3169 .- 0378-4274. ; 21:2, s. 213-218
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Journal article (peer-reviewed)abstract
- Age- and weight-matched groups of mice were enclosed in airtight chambers and exposed to clean, filtered air for 1 month. At the end of the exposure period, body, liver and spleen weights and plasma butyrylcholinesterase (BuChE) activity were measured. More than twice as many significant differences in these parameters occurred compared with the expected results if only random differences existed between the groups. Thus, isolation of animal groups for extended periods of time in inhalation experiments alone may lead to differences in various biological parameters. When testing the effects of unknown substances such differences may be mistaken for reactions to the test agent, which actually may have no effect.
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| 5. |
- Kjellstrand, Per, et al.
(author)
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Sensitivity of mongolian gerbils to trichloroethylene exposure during neonatal growth
- 1982
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In: Toxicology Letters. - : Elsevier BV. - 1879-3169 .- 0378-4274. ; 14:1-2, s. 97-101
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Journal article (peer-reviewed)abstract
- Continuous exposure of young mongolian gerbils to trichloroethylene (230 ppm) was started at different times during the first month of life. The onset of exposure was accompanied by an increased number of deaths among the pups and by an immediate reduction in growth rate. The proportion of dead pups was greatest when exposure was started at birth, and decreased rapidly with increasing age at onset of exposure. Growth rate was partially restored approx. 1 week after the onset of exposure. After weaning the effect of the exposure on growth decreased, and the variation in the effect among different litters was considerably reduced. The enhanced sensitivity of the pups to trichloroethylene (TCE) exposure is believed to be due to a disturbance in the mother-offspring relationship.
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| 8. |
- Berglund, M, et al.
(author)
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Metal-bone interactions
- 2000
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In: Toxicology letters. - : Elsevier BV. - 0378-4274. ; 112112-113, s. 219-225
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Journal article (peer-reviewed)
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| 13. |
- Gustafsson, JA
(author)
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Receptor-mediated toxicity
- 1995
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In: Toxicology letters. - : Elsevier BV. - 0378-4274. ; 82-382-83, s. 465-470
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Journal article (peer-reviewed)
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| 17. |
- HEMMINKI, K
(author)
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DNA adducts in biomonitoring
- 1995
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In: Toxicology letters. - : Elsevier BV. - 0378-4274. ; 77:1-3, s. 227-229
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Journal article (peer-reviewed)
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| 30. |
- Rudén, Christina, et al.
(author)
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How accurate are the European Union's classifications of chemical substances
- 2003
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In: Toxicology Letters. - : Elsevier BV. - 0378-4274 .- 1879-3169. ; 144:2, s. 159-172
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Journal article (peer-reviewed)abstract
- The European Commission has decided on harmonized classifications for a large number of individual chemicals according to its own directive for classification and labeling of dangerous substances. We have compared the harmonized classifications for acute oral toxicity to the acute oral toxicity data available in the RTECS database. Of the 992 substances eligible for this comparison, 15% were assigned a too low danger class and 8% a too high danger class according to the RTECS data. Due to insufficient transparency-scientific documentations of the classification decisions are not available-the causes of this discrepancy can only be hypothesized. We propose that the scientific motivations of future classifications be published and that the apparent over- and underclassifications in the present system be either explained or rectified, according to what are the facts in the matter.
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| 31. |
- Silva, A. V., et al.
(author)
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Dose-dependent toxicological effects in rats following a 90-day dietary exposure to PCB-156 include retinoid disruption
- 2021
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In: Toxicology Letters. - : Elsevier. - 0378-4274 .- 1879-3169. ; 350:Suppl., s. S163-S163
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Journal article (other academic/artistic)abstract
- The toxicity of PCB-156 (2,3,3¢,4,4¢,5-hexachlorobiphenyl) was investigated in rats following subchronic dietary exposure. Groups of 10 male and 10 female Sprague-Dawley rats were administered PCB in the diet at 0, 0.01, 0.1, 1 or 10 ppm for 13 weeks. Results were analysed by group-wise comparison and benchmark dose-modelling. The latter revealed ose-related decreases of final body weight, growth rate and thymus weight. Additionally, rats receiving PCB-156 showed dose-dependent weight increases of liver, lungs and kidneys. Biochemical changes included increases in liver EROD, PROD and UD-PGT enzymatic activities, as well as increases in uro-porphyrin. Retinoid (Vitamin A) quantification showed a clear and treatment-related reduction of the levels in the liver and lungs, as well as increased levels in the kidneys. A owest-observable-adverse-effect level (LOAEL) of 0.01 ppm was established, based on effects in the liver apolar retinoids concentration, corresponding to dietary exposure of 0.7 and 0.8 μg PCB-156/kg body weight per dayin male and female rats, respectively. Benchmark dose-modelling corroborated effects in the retinoid system, in both sexes, at even lower intake levels. The lower confidence limit (BMDL) for a 5% decrease in the concentration of liver apolar retinoids was 0.00086 (males) and 0.00068 ppm (fe-males), corresponding to a daily exposure of 0.06 μg PCB-156/kg body weight for both sexes. This BMDL5 is approximately 10-fold lower than the LOAEL for PCB-156. Based on the retinoid system’s susceptibility to PCB-156 exposure, we recommend effects on this system to be considered as critical for risk assessment of PCB-156 and other PCB congeners.
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| 43. |
- Alenius, H
(author)
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Systems Biology as ToxicOmics
- 2016
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In: TOXICOLOGY LETTERS. - : Elsevier BV. - 0378-4274. ; 259, s. S70-S71
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Conference paper (other academic/artistic)
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| 48. |
- Ali, Imran, et al.
(author)
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From pure compounds to complex exposure : Effects of dietary cadmium and lignans on estrogen, epidermal growth factor receptor, and mitogen activated protein kinase signaling in vivo.
- 2016
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In: Toxicology Letters. - : Elsevier BV. - 0378-4274 .- 1879-3169. ; 253
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Journal article (peer-reviewed)abstract
- Exposure to environmental endocrine active compounds correlates with altered susceptibility to disease in human populations. Chemical risk assessment is single compound based, although exposure often takes place as heterogeneous mixtures of man-made and natural substances within complex matrices like diet. Here we studied whether the effects of cadmium and enterolactone on endocrine endpoints in dietary exposure can be predicted based on pure compound effects. Ovariectomized estrogen reporter ERE-luciferase (ERE-luc) mice were maintained on diets that intrinsically contain increasing concentrations of cadmium and enterolactone precursors for three and 21 days. The activation of the ERE-luc, epidermal growth factor receptor (EGFR), mitogen activated protein kinase (MAPK)-ERK1/2, and classical estrogen responses were measured. Interactions between the diets and endogenous hormone were evaluated by challenging the animals with 17β-estradiol. Compared to animals on basal purified diet, mice consuming experimental diets were exposed to significantly higher levels of cadmium and enterolactone, yet the exposure remained comparable to typical human dietary intake. Surprisingly, we could not detect effects on endpoints regulated by pure enterolactone, such as ERE-luc activation. However, cadmium accumulation in the liver was accompanied with activation of EGFR and MAPK-ERK1/2 in line with our earlier CdCl2 studies. Further, attenuation of 17β-estradiol-induced ERE-luc response in liver by experimental diets was observed. Our findings indicate that the exposure context can have substantial effects on the activity of endocrine active compounds in vivo. Thus, whenever possible, a context that mimics human exposure should be tested along with pure compounds.
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