Inhaled airborne particulate matter (PM) represents a potentially significant health hazard to humans. Exposure to PM strongly correlates with pulmonary inflammation and incidences of severe respiratory distress, including increased hospital admissions for breathing disorders, asthma, emphysema, and chronic bronchitis. PM generated from the combustion of fuel oils and coals contain a number of water-soluble transition metals including Fe, V, and Zn.
We have evaluated the impact of PM types with varying composition collected from the combustion of oils and coals on the health and metabolism of lung cell cultures. Three colorimetric assays (sulforhodamine B (SRB), Janus green, and MTT) have been adapted to quantify the impact of PM on rat lung alveolar type II epithelial cells (RLE-6TN cells). The PM toxicity metrics evaluated were inhibition of cell proliferation (SRB and Janus green) and inhibition of cellular metabolism (MTT). Cell proliferation is inhibited in a consistent dose-dependent manner by PM concentrations from 25 to 250 μg/ml. At a level of 100 μg/ml, oil-derived PM diminishes cell metabolism by as much as 40% relative to controls; the degree of inhibition is strongly dependent on PM particle size and metal content. Conversely, coal-derived PM at the same dosage diminishes cell metabolism by no more than 20% relative to controls. All three assays provide highly repeatable results and consistent toxicity rankings of the PMs evaluated. Overall, metabolic inhibition as measured by the MTT assay was deemed the most appropriate metric for PM toxicity, primarily due to its applicability with in vivo-like confluent cell monolayers. 相似文献
We report the first molecular prenatal diagnosis of 3-hydroxy-3-methylglutaryl CoA lyase (HL) deficiency. The proband had a classic but severe presentation with hypoketotic hypoglycaemia and acidosis, secondary mental retardation, and epilepsy, and HL deficiency was documented in cultured fibroblasts. We found him to be homozygous for the frameshift mutation N46fs (+1), which yields a distinct pattern on single-strand conformation polymorphism (SSCP) analysis. In two subsequent pregnancies, molecular prenatal diagnosis was performed using SSCP. In the first, chorionic villus biopsy was normal. In the second pregnancy, amniocentesis revealed an affected fetus. In both pregnancies, the diagnosis was confirmed enzymatically. HL activity was less than 7 per cent of control values in amniocytes and fetal liver of the affected pregnancy. In the second pregnancy, amniotic fluid metabolite measurements by stable isotope dilution-selected ion monitoring mass spectrometry showed greater than 100-fold increases of 3-hydroxy-3-methylglutaric acid and of 3-methylglutaconic acid levels compared with controls. 相似文献
The peroxynitrite/porphyrin biomimetic system was established to investigate the effects of peroxynitrite on benzo[a]pyrene (B[a]P) metabolism. Three model systems consisting of different iron porphyrins were compared, and the results showed that the peroxynitdte/T(p-Cl)PPFeCl system was the highest catalytic efficiency in the metabolism of B [a]P. We analyzed the B [a]P metabolites produced from this system by RP-HPLC method and firstly identified the formation of nitrobenzo[a]pyrenes which are the special metabolites of B [a]P induced by peroxynitrite. 相似文献
Summary. Nicotine tolerance is well known for Manduca sexta. It also occurs in several other sphingids of the subfamilies Macroglossinae and Sphinginae. Only members of the subfamily
Smerinthinae appear to be more susceptible to nicotine intoxication. Phylogenetic trees have been reconstructed from mitochondrial
16S rDNA and nuclear DNA to map nicotine tolerance.?The nicotine binding site of both α-subunits of nicotinic acetylcholine receptors (nAChR) have been amplified and sequenced. No apparent amino acid substitution
can be seen in the putative nicotine binding site of the α-subunits of nAChR from nicotine tolerant and nicotine sensitive sphingids. Thus, a simple target-site modification can be
ruled out as a cause for nicotine tolerance. This finding agrees with feeding experiments: larvae of M. sexta and other sphingids of the Macroglossinae and Sphinginae not only tolerated nicotine, but also many other alkaloids that
affect neuroreceptors other than acetylcholine receptors (nAChR, mAChR).?Only 10 to 20% of nicotine injected into larvae of
nicotine-tolerant taxa could be recovered later as free nicotine, nicotine N-oxide or cotinine, i.e., 80 to 90% must have been converted to polar conjugates or degradation products which are not detectable with the methods
applied. Usually more than 98% of the recoverable alkaloids were found in the faeces. Excretion reached a maximum 6 h after
injection in tolerant taxa. Larvae of Manduca sexta, which were reared on a nicotine-rich diet, showed higher nicotine degradation and faster nicotine elimination than na?ve
larvae. Application of the cytochrome P450 inhibitor SKF 525A (proadifen) reduced the formation of nicotine N-oxide and the rate of alkaloid degradation. Thus, an
inducible detoxification mechanism, coupled with a rapid and inducible excretion, appear to be a strategy in Sphingidae that
helps them to live on host plants rich in otherwise toxic secondary metabolites.
Received 23 March 2001; accepted 4 August 2001. 相似文献
Summary. We investigated the effects of four chemically characterised galloylglucoses (GGs, a subgroup of hydrolysable tannins) and
their hydrolysis product, gallic acid (GA), on consumption and performance of larvae of the autumnal moth Epirrita autumnata. Larvae were fed with birch (Betula pubescens) leaves that had been painted individually with each of the compounds at two levels, 5 and 20 mg/g. In addition, we investigated
the fates of the leaf-painted GGs and GA in the E. autumnata digestive tract by comparing phenolics in leaves consumed and in faeces. In general, GGs reduced leaf consumption by E. autumnata during the second and fourth instars, although there was high compound- and instar-specific variation. However, GGs did not
affect the leaf consumption rates by the most voracious fifth instar larvae. This resulted in approximately the same loss
of total biomass by the experimental tree, regardless of the nature and level of GGs enriched to its foliage. The characteristic
fate of hydrolysable tannins, i.e. hydrolysis, was evidenced in the larval digestive tract for three of the four leaf-painted
GGs. In addition to hydrolysis, the almost total absence of GGs in larval faeces was presumably related to the oxidation of
GGs. The dose-dependent excretion percentage of ingested GA showed that it's faecal content should not be used, although it
commonly is, to calculate the level of GG hydrolysis. Moreover, by comparing the non-uniform appearance of faecal tetragalloylglucoses,
whether ingested as such or hydrolysed from pentagalloylglucose, we concluded that a major part of oxidation of GGs occurs
before their hydrolysis in the digestive tract of E. autumnata. Criticism against the common use of tannic acid, a heterogeneous mixture of GA and GGs, in ecological studies is presented.
Received 15 May 2002; accepted 16 July 2002 相似文献
The present paper describes the isolation and identification of a new metabolite of hexachlorobenzene (HCB), which is N-acetyl-S-(pentachlorophenyl)cysteine (PCC), frequently named pentachlorophenylmercapturic acid or 2-acetamido-3-(pentachlorophenylmercapto)propionic acid. PCC has been detected in and identified from rat urine. The syntheses of PCC and the isomeric tetrachlorophenylmercapturic acids (TCC) are described in the following paper. 相似文献