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The in vivo metabolism of benzo[a]pyrene studied by chromatography in combination with mass spectrometry /Yang, Yang, January 1900 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.
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The physiology of mycorrhizal Lolium multiflorum in the phytoremediation of petroleum hydrocarbon-contaminated soilAlarcon, Alejandro 02 June 2009 (has links)
Arbuscular mycorrhizal fungi (AMF) can play an important role in the
phytoremediation of petroleum hydrocarbon (PH)-contaminated soil. However, little is
known about the effects of AMF in combination with biostimulation via fertilization or
bioaugmentation with hydrocarbonoclastic microorganisms, during phytoremediation of
PH in soils.
This research evaluated the influence of the AMF Glomus intraradices and
inorganic fertilization on growth and physiological responses of Lolium multiflorum Lam.
cv. Passarel Plus during phytoremediation of soil contaminated with Arabian medium
crude oil (ACO). Also determined was the interaction of AMF with the
hydrocarbonoclastic bacterium, Sphingomonas paucimobilis EPA505 (Sp), and the
filamentous fungus, Cunninghamella echinulata var. elegans ATCC-36112 (Ce), on
growth and selected physiological responses of L. multiflorum during phytoremediation
of soil contaminated with benzo[a]pyrene (BaP) or ACO.
This research provides evidence that AMF enhance the phytoremediation of
petroleum hydrocarbons in soils when inoculated with L. multiflorum. The concentration
of petroleum hydrocarbons in soil was a determining factor of potential benefits of AMF on L. multiflorum. Low (3000 mg·kg-1) or high (15000 mg·kg-1) concentrations of ACO
resulted in limited benefits of AMF on plant growth, physiology, and degradation of
ACO in soil. However, when plants were exposed to an intermediate ACO concentration
in soil (6000 mg·kg-1), AMF plants had enhanced growth, physiological responses, and
greater ACO-degradation than non-AMF plants. The AMF symbiosis in roots of plants
was observed at all concentrations of ACO-contaminated soil.
This research is one of the first reports demonstrating the benefits of AMF on the
degradation of benzo[a]pyrene or ACO, alone or in combination, with the
hydrocarbonoclastic microorganisms. Thus, AMF resulted in a beneficial synergism with
the hydrocarbonoclastic microorganisms, particularly during ACO-degradation in the
rhizosphere of L. multiflorum. Hydrocarbonoclastic microorganisms had no negative
effects on AMF colonization.
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Comparison of the acute effects of benzo[a]pyrene on cardiorespiratory function and fitness in adult zebrafish (Danio rerio) following i.p. injection or aqueous exposure2015 May 1900 (has links)
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants. There are numerous studies reporting developmental cardiac toxicity in multiple fish species due to PAH exposure. However, there are relatively few instances where the effects of acute PAH exposure in adult fish have been characterized. Furthermore, the majority of experiments comparing PAH toxicity with exposure route in adult fish focus on CYP1A gene expression or enzyme activity, while there is a lack of information about the possible pathophysiological effects. Therefore, the overall objective of this thesis was to characterize the sublethal effects of benzo[a]pyrene (BaP), a prototypical PAH, on adult zebrafish (Danio rerio) cardiorespiratory function and fitness following acute exposure by two different routes. In the first experiment, adult zebrafish were intraperitoneally (i.p.) injected twice (one injection/24 hr) with increasing concentrations of BaP (0.1, 10, and 1000 μg/kg) and compared to corresponding dimethylsulfoxide (DMSO) controls. In a second set of experiments, adult zebrafish were aqueously exposed to BaP (static, renewal at 24 hr; 16.2 and 162 μg/L) and compared to DMSO controls. Following 48 hr exposure, one group of fish (n=10/treatment group) were subjected to swimming performance tests to assess critical swimming speed (Ucrit), oxygen consumption rate (MO2), cost of transport (COT), standard metabolic rate (SMR), active metabolic rate (AMR), and factorial aerobic scope (F-AS). Another group of fish (n=12/treatment group) were subjected to echocardiography following 48 hr BaP exposure to evaluate cardiac function. Following echocardiography analysis, samples were collected for parent compound (BaP) body burden and CYP1A mRNA induction analysis.
48 hr BaP injection resulted in significant sublethal effects on adult zebrafish cardiorespiratory function. Oxygen consumption (MO2) was increased at three swimming speeds in injected BaP groups compared to control. In contrast, aqueously BaP-exposed fish showed increased MO2 only at the single lowest swim speed. COT was also similarly increased for both exposure routes. SMR was elevated with both exposure routes, while AMR remained unchanged. This resulted in a significant decrease in F-AS for all treatment groups compared to corresponding controls with both exposure routes.
Cardiac function was significantly affected by both routes of BaP exposure. Ventricular heart rate was significantly decreased in BaP-exposed fish, both injected and aqueously-exposed. However, stroke volume was decreased only in fish aqueously exposed to BaP, which resulted in significantly reduced cardiac output with that exposure route. In contrast, the ratio of atrial to ventricular heart rate (AV ratio) was increased only in fish i.p. injected with BaP, indicating the possibility of cardiac arrhythmias occurring. Analysis of BaP body burdens in fish tissue allowed for identification of an overlapping dose group between exposure routes, through which comparisons of cardiotoxicity were then made. This comparison revealed slight differences in cardiotoxicity between exposure routes. BaP-injected fish suffered from more severe bradycardia than aqueously exposed fish. Furthermore, cytochrome P4501A (CYP1A) mRNA levels in liver and heart tissue showed more significant increases in injected fish, while skeletal muscle CYP1A was increased only following aqueous exposure.
In conclusion, acute BaP exposure caused metabolic alterations and impaired cardiorespiratory function in adult zebrafish regardless of exposure route. Interestingly, the primary mechanism behind these effects appeared to differ slightly with exposure route. These results suggest that acute BaP exposure may have negative effects on adult fish survivability in the environment. Overall, this work provides valuable insight into the pathophysiogical consequences of acute PAH exposure in adult stage fish.
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Mechanism of benzo(a)pyrene-induced accumulation of p53 tumour suppressor protein in mouseSerpi, R. (Raisa) 13 June 2003 (has links)
Abstract
The tumour suppressor gene TP53 is the most commonly mutated gene in human cancers. The protein it codes, p53, becomes activated as a response to stress signals. When activated, p53 binds to DNA and affects the transcription of its target genes. They then cause cell cycle arrest, DNA repair and/or induction of programmed cell death, thus preventing mutations and cancer. Specific mutations in TP53 are associated with exposure to certain carcinogens, such as polycyclic aromatic hydrocarbons (PAHs). These environmental chemical carcinogens are formed through incomplete combustion of organic material. Benzo(a)pyrene (BP) is commonly used as a model compound for PAH carcinogenesis. BP causes accumulation of p53, but the mechanism of accumulation is not known. The aim of this study was to gain more insight into the p53 protein in the first phases of PAH carcinogenesis in vivo in mouse, using BP as the model compound.
Mice from the inbred C57BL/6 strain were treated topically or intraperitoneally with BP or were exposed to cigarette smoke inhalation. The amount of p53 protein was studied by immunoblotting, immunohistochemistry and immuno electron microscopy, and the mdm2, p21 and p19ARF proteins were studied by immunoblotting. The binding of BP to DNA was measured by synchronous fluorescence spectrophotometry.
The p53 protein was induced in vivo in skin and lung after BP treatment and in lung after cigarette smoke treatment. An increase in p53 was associated with an increase in the amount of BP-DNA adducts. In skin, the induction of p53 was accompanied by induction of the p21 and mdm2 proteins, which are transcriptional targets of p53. This indicates that the in vivo induced p53 is a wild-type protein and functional. In lungs, the induction of p53 was accompanied by a decrease of mdm2 and an increase of p19ARF. These results confirm that BP is metabolized and binds to DNA in mouse tissues and indicate that BP-DNA adducts are the trigger for p53 protein induction. The in vivo regulation of the p53 protein is different in different tissues of C57BL/6 mouse.
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ALTERED GENE EXPRESSION: A MECHANISM OF REPRODUCTIVE TOXICITY IN ZEBRAFISH (DANIO RERIO) EXPOSED TO BENZO[a]PYRENEHoffmann, Jennifer 19 August 2004 (has links)
No description available.
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Characterization of toxicological effects of a novel in vivo benzo[a]pyrene metabolite in colonic cells /Nordling, Mirjam, January 2004 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.
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Mechanisms of environmental tobacco smoke and benzo[a]pyrene induced cardiovascular injury and the protective role of resveratrolAl-Dissi, Ahmad 21 March 2011
Despite extensive research, the mechanisms behind cardiovascular effects of subchronic environmental tobacco smoke (ETS) remain unclear, but may be related to ETS-induced inflammation and oxidative stress. Additionally, the protective role of resveratrol (RES), a natural antioxidant available in red grapes, is controversial. We hypothesized that the polycyclic aromatic hydrocarbon (PAH) component of ETS is responsible for causing adverse cardiovascular effects. We also hypothesized that the administration of RES is protective against the adverse cardiovascular effects of ETS. In order to address these hypotheses, male juvenile pigs (4-weeks old) were exposed to ETS or ambient air for 28 consecutive days (1 hr/day) and effects compared to 7 days of i.v. injection of the PAH, benzo-a-pyrene (BAP; 5 mg/kg daily). In another experiment, pigs were sham-exposed or ETS-exposed, with or without oral RES treatment (5mg/kg daily). In all experiments, endothelial and left ventricular function were assessed by flow mediated dilation (FMD), and echocardiography, respectively, while blood pressure was evaluated by oscillometry. At the termination of each experiment, serum nitrotyrosine, total nitrate/nitrite (NOx) and C-reactive protein (CRP) were measured as well as hepatic and pulmonary ethoxyresorufin-o-deethylase (EROD) activity to indicate cytochrome P450 1A1 (CYP1A1) expression. Finally, the correlation between pulmonary inflammation and adverse cardiovascular effects was investigated by measuring total and differential white blood cell (WBC) count as well as leukocyte elastase activity in bronchoalveolar lavage fluid at the termination of each experiment. ETS exposure, but not BAP treatment, resulted in a significant impairment of FMD (P<0.0001) and increased left ventricular end diastolic volume (P=0.0032). Cotreatment with RES failed to restore the ETS induced impairment of FMD (P>0.05). However, a trend pointing to an increase in ejection fraction (EF) was noted (P=0.072). ETS, BAP and RES treatments failed to have any effect on blood pressure (P>0.05). BAP injection caused a significant increase in serum nitrotyrosine (P=0.0146) and CRP (P=0.012), but not serum NOx levels (P>0.05). In contrast, ETS exposure resulted in a significant increase in CRP serum levels (P=0.0092), a trend pointing to increased serum nitrotyrosine (P=0.105), and no change in serum NOx levels (P>0.05). The increased nitrotyrosine and CRP with ETS exposure was not reversed by RES administration (P>0.05). ETS exposure increased EROD activity in the lung (P=0.0093), but not the liver (P=0.12). In contrast, BAP treatment had the opposite effect (lung EROD: P=0.621, liver EROD: P=0.01), while RES administration had no effect (P>0.05). ETS exposure (P=0.0139), but not BAP treatment (P=0.723), resulted in increased WBC count in BAL fluid which was not affected by RES administration (P>0.05). These results show that ETS exposure causes lung inflammation, systemic inflammation, oxidative stress-mediated inactivation of nitric oxide and impaired endothelial function. In contrast, BAP failed to alter endothelial function, downstream of the lung, despite systemic inflammation and increased oxidative stress. Furthermore, RES failed to restore endothelial function, or decrease systemic inflammation and oxidative stress. Taken together, these results suggest either that pulmonary inflammatory responses or pulmonary increases in CYP1A1 activity may be more important links to endothelial dysfunction than systemic inflammation and nitric oxide bioactivity. The beneficial effects of RES by itself are manifested only at the cardiac level by improving the ejection fraction, but the work in this thesis failed to detect any ability of RES to ameliorate ETS cardiovascular effects.
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Mechanisms of environmental tobacco smoke and benzo[a]pyrene induced cardiovascular injury and the protective role of resveratrolAl-Dissi, Ahmad 21 March 2011 (has links)
Despite extensive research, the mechanisms behind cardiovascular effects of subchronic environmental tobacco smoke (ETS) remain unclear, but may be related to ETS-induced inflammation and oxidative stress. Additionally, the protective role of resveratrol (RES), a natural antioxidant available in red grapes, is controversial. We hypothesized that the polycyclic aromatic hydrocarbon (PAH) component of ETS is responsible for causing adverse cardiovascular effects. We also hypothesized that the administration of RES is protective against the adverse cardiovascular effects of ETS. In order to address these hypotheses, male juvenile pigs (4-weeks old) were exposed to ETS or ambient air for 28 consecutive days (1 hr/day) and effects compared to 7 days of i.v. injection of the PAH, benzo-a-pyrene (BAP; 5 mg/kg daily). In another experiment, pigs were sham-exposed or ETS-exposed, with or without oral RES treatment (5mg/kg daily). In all experiments, endothelial and left ventricular function were assessed by flow mediated dilation (FMD), and echocardiography, respectively, while blood pressure was evaluated by oscillometry. At the termination of each experiment, serum nitrotyrosine, total nitrate/nitrite (NOx) and C-reactive protein (CRP) were measured as well as hepatic and pulmonary ethoxyresorufin-o-deethylase (EROD) activity to indicate cytochrome P450 1A1 (CYP1A1) expression. Finally, the correlation between pulmonary inflammation and adverse cardiovascular effects was investigated by measuring total and differential white blood cell (WBC) count as well as leukocyte elastase activity in bronchoalveolar lavage fluid at the termination of each experiment. ETS exposure, but not BAP treatment, resulted in a significant impairment of FMD (P<0.0001) and increased left ventricular end diastolic volume (P=0.0032). Cotreatment with RES failed to restore the ETS induced impairment of FMD (P>0.05). However, a trend pointing to an increase in ejection fraction (EF) was noted (P=0.072). ETS, BAP and RES treatments failed to have any effect on blood pressure (P>0.05). BAP injection caused a significant increase in serum nitrotyrosine (P=0.0146) and CRP (P=0.012), but not serum NOx levels (P>0.05). In contrast, ETS exposure resulted in a significant increase in CRP serum levels (P=0.0092), a trend pointing to increased serum nitrotyrosine (P=0.105), and no change in serum NOx levels (P>0.05). The increased nitrotyrosine and CRP with ETS exposure was not reversed by RES administration (P>0.05). ETS exposure increased EROD activity in the lung (P=0.0093), but not the liver (P=0.12). In contrast, BAP treatment had the opposite effect (lung EROD: P=0.621, liver EROD: P=0.01), while RES administration had no effect (P>0.05). ETS exposure (P=0.0139), but not BAP treatment (P=0.723), resulted in increased WBC count in BAL fluid which was not affected by RES administration (P>0.05). These results show that ETS exposure causes lung inflammation, systemic inflammation, oxidative stress-mediated inactivation of nitric oxide and impaired endothelial function. In contrast, BAP failed to alter endothelial function, downstream of the lung, despite systemic inflammation and increased oxidative stress. Furthermore, RES failed to restore endothelial function, or decrease systemic inflammation and oxidative stress. Taken together, these results suggest either that pulmonary inflammatory responses or pulmonary increases in CYP1A1 activity may be more important links to endothelial dysfunction than systemic inflammation and nitric oxide bioactivity. The beneficial effects of RES by itself are manifested only at the cardiac level by improving the ejection fraction, but the work in this thesis failed to detect any ability of RES to ameliorate ETS cardiovascular effects.
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Acute Toxicity and Sub-Lethal Effects of Non-Point Source Pollutants on InvertebratesRomano, Jocelyn Ann 07 May 2007 (has links)
Non-point source pollution is not generated from any single source, rather can
arise from a mixture of agricultural, residential, and industrial activities. As a result of
these activities millions of tons of chemicals enter into aquatic environments annually
with the potential to disrupt the fragile ecosystems existing within. Common
anthropogenic compounds most frequently seen in estuarine environments include
pesticides, antifoulants, polycyclic aromatic hydrocarbons (PAH), and industrial
solvents.
This dissertation examines the acute toxicity and sub-lethal effects of diuron,
CuPT, B(a)P, and styrene in the mud snail, Ilyanassa obsoleta, the American oyster,
Crassostrea virginica, the sea urchin, Lytechinus variegatus, and/or the barnacle,
Amphibalanus (= Balanus) amphitrite. In addition, the general effects of non-point source
pollution within the Rachel Carson Estuarine Research Reserve (RCERR) were examined
at six sites in order to gain a better understanding of the current health of this unique
habitat.
Of the four compounds tested, only the industrial solvent, styrene, resulted in an
LC50 (1341 µg L-1, I. obsoleta) that was within the range of currently reported
environmental levels. Diuron and CuPT did not elicit mortality at environmentally
relevant concentrations, but did significantly reduce fecundity in I. obsoleta and C.
virginica and fertilization success and larval development in L. variegatus. The only
notable sub-lethal effect elicited by the PAH, benzo(a)pyrene, was a significant decrease
in egg capsule production by I. obsoleta following exposure to concentrations as low as
50 µg L-1.
Within the RCERR, animals from Sites 4, 5, and 6 were observed to have
significant differences with respect to fecundity, condition index, and/or ECOD activity
when compared to conspecific organisms from control Site 1. This is most likely a
consequence of their proximity to anthropogenic sources. Large variation in mortality
(15-98.9%) was observed when families of A. amphitrite from a single population where
exposed to CuPT.
It is often difficult to extrapolate data from laboratory findings into natural
populations. Frequently the organisms used under laboratory conditions are genetically
very similar, while field population can vary with anthropogenic exposure. Caution
must be taken when developing protocols for risk assessment to ensure that actual
environmental conditions are being represented. / Dissertation
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Toxicity Analysis of Polycyclic Aromatic Hydrocarbon MixturesNaspinski, Christine S. 16 January 2010 (has links)
Polycyclic aromatic hydrocarbons (PAHs) are widely distributed in the
environment and are generated by many sources. Though the potential of PAH-rich
mixtures to cause health effects has been known for almost a century, there are still
unanswered questions about the levels of PAHs in the environment, the potential for
human exposure to PAHs, the health effects associated with exposure, and how genetic
susceptibility influences the extent of health effects in individuals.
The first objective of this research was to quantify concentrations of PAHs in
samples of settled house dust collected from homes in Azerbaijan, China, and Texas.
The trends of PAH surface loadings and percentage of carcinogenic PAHs were China
> Azerbaijan > Texas, indicating that the risk of health effects from exposure to PAHs in
house dust is highest in the Chinese population and lowest in the Texas population.
PAHs in China and Azerbaijan were derived mainly from combustion sources; Texas
PAHs were derived from unburned fossil fuels such as petroleum.
The second objective of this research was to investigate the effect of pregnane
X receptor (PXR) on the genotoxicity of benzo[a]pyrene (BaP). BaP treatment resulted
in significantly lower DNA adduct levels in PXR-transfected HepG2 cells than in
parental HepG2 cells. Total GST enzymatic activity and mRNA levels of several
metabolizing enyzmes were significantly higher in cells overexpressing PXR. These
results suggest that PXR protects cells against DNA damage by PAHs such as BaP,
possibly through a coordinated regulation of genes involved in xenobiotic metabolism.
The third objective of this research was to investigate biomarkers of exposure in
house mice (Mus musculus) exposed to PAH mixtures in situ. Mice and soil were
collected near homes in Sumgayit and Khizi, Azerbaijan. Mean liver adduct levels were
significantly higher in Khizi than in Sumgayit. Mean lung and kidney adduct levels were similar in the two regions. The DNA lesions detected may be a combination of
environmentally-induced DNA adducts and naturally-occurring I-compounds. PAHs
were present at background levels in soils from both Khizi and Sumgayit. It appears
that health risks posed to rodents by soil-borne PAHs are low in these two areas.
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