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Ian R Phillips

Publications and source records attributed to Ian R Phillips.

11 recordsLinked to original sources

Tributyltin partitioning in sediments: effect of aging.

The effect of aging on the solid/pore-water partitioning and desorption behaviour of tributyltin (TBT) in sediments was examined. Three sediment samples with contrasting physical and chemical properties were spiked with 10 mg/kg TBT and aged under sterile conditions for periods of time ranging from 1 to 84 days. Aging had a negligible effect on partitioning and desorption behaviour in a sandy sample with very low organic carbon content (0.2% w/w). In contrast, for samples with larger amounts of organic carbon (2.6% and 4.8% w/w), aging caused substantial increases in TBT sorption. For these samples, apparent distribution coefficients (KD,app) obtained from sequential 2 h desorption experiments also exhibited a twofold increase between spiked sediments subjected to aging for 1 day and 84 days. This study demonstrates that aging effects may be an important aspect of TBT fate in contaminated sediments.

Adsorption↗

Trace metal distribution and enrichment in benthic, estuarine sediments: Southport Broadwater, Australia.

The distribution and enrichment of selected trace metals (Cd, Cr, Cu, Ni, Pb, Sn, Zn) in benthic sediments of the Southport Broadwater, a semi-enclosed coastal body of water adjacent to the Gold Coast city, south-eastern Queensland, Australia, was studied with the objective of assessing the extent and degree of sediment contamination. Sediment samples from the 0-10 cm and 10-20 cm depth intervals of 32 sites within the Southport Broadwater and surrounding residential canals were analysed for particle size distribution, pH, organic C and 'near-total' major (Al, Ca, Fe, Mn) and trace (Cd, Cr, Cu, Ni, Pb, Sn, Zn) metal contents. Sediment contamination for each trace metal was assessed by (1) comparison with Australian sediment quality guidelines, (2) calculation of the index of geoaccumulation based on regional background values, and (3) geochemical normalisation against Al (i.e. the abundance of alumino-silicate clay minerals). Based on this approach, the results indicate that submerged sediments in the study area are not presently enriched with Cd, Cr or Ni, with the spatial distribution of these metals being very well explained by the abundance of alumino-silicate clay minerals. However, several sites were strongly enriched with Cu, Pb, Sn and Zn, arising from sources related to either urban runoff or vessel maintenance activities. The study indicates that several varying approaches are needed for a satisfactory assessment of contaminant enrichment in estuarine sediments.

Aluminum Silicates↗

Sorption and desorption behavior of tributyltin with natural sediments.

Tributyltin (TBT) sorption to four natural sediment samples in artificial seawater was examined under a range of modified pH and salinity conditions. Three of the sediment samples were relatively pristine with regard to TBT contamination, but the fourth was a TBT-contaminated sediment from a commercial marina. Sorption of TBT was described well by linear sorption isotherms, with distribution coefficients ranging from 6.1 to 5210 L/kg depending on the pH and salinity. The sediment organic C content and particle size distribution were important determinants of sorption behavior. The presence of resident TBT in the contaminated marina sediment caused a substantial reduction in further TBT sorption. Desorption of TBT from the marina sediment was described by relatively large observed distribution coefficients ranging from 5100 to 9400 L/kg, suggesting that aging effects may reduce sorption reversibility. Increased artificial seawater salinity generally reduced TBT sorption at pH 4 and 6, but enhanced TBT sorption at pH 8. Regardless of salinity, maximum sorption of TBT was observed at pH 6, which is attributed to an optimal balance between the abundance of cationic TBT+ species and deprotonated surface ligands. Consideration of aqueous TBT speciation along with octanol-water partitioning behavior suggests that hydrophobic partitioning of TBTCl(0) to nonpolar organic matter was important for pH < 6, while partitioning of TBTOH(0) was important at higher pH.

Adsorption↗

In-situ partitioning of butyltin compounds in estuarine sediments.

The in-situ solid/pore-water partitioning of tributyltin (TBT), dibutyltin (DBT) and monobutyltin (MBT) was determined for an estuarine sediment profile collected from a commercial marina. Total butyltin levels exceeded sediment quality guideline values, and were 220-8750 microg/kg for TBT, 150-5450 microg/kg for DBT and 130-4250 microg/kg for MBT. Pore-water butyltin concentrations ranged from 0.05 to 2.35 microg/l for TBT, 0.07-3.25 microg/l for DBT, and 0.05-0.53 microg/l for MBT. The partitioning of butyltin compounds between the sediment solid-phase and pore-water was described by an organic carbon normalised distribution ratio (D(OC)). The observed D(OC) values were similar for TBT, DBT and MBT, and were 10(5)-10(6) l/kg. Values for the Butyltin Degradation Index (BDI) were larger than 1 at depths greater than 10 cm below the sediment/water-column interface. This indicates that substantial TBT degradation has occurred in the sediments, and suggests that natural attenuation may be a viable sediment remediation strategy.

Carbon↗

Cell-, tissue-, sex- and developmental stage-specific expression of mouse flavin-containing monooxygenases (Fmos).

The cell-, tissue-, sex- and developmental stage-specific expression profiles of five members of the flavin-containing monooxygenase (FMO) family, FMO1, 2, 3, 4 and 5, were investigated in 129/SV mice, using isoform-specific antisense RNA probes. In situ hybridization localized FMO1 and 5 mRNAs to the perivenous, and FMO 2, 3 and 4 mRNAs to the periportal, regions of the liver. In kidney, each FMO mRNA is localized to the distal and proximal tubules and collecting ducts; FMO1 mRNA is present also in the glomerulus. In lung, FMO1 and 3 mRNAs are expressed in the terminal bronchiole, and FMO1 mRNA also in the alveoli. FMO1 mRNA is present in neurons of the cerebrum and in the choroid plexus. RNase protection assays showed that the most abundant isoform in newborn liver, lung, kidney and brain, and in adult lung and kidney is FMO1, but in adult liver FMO5 is present in greatest amounts. In liver, lung and kidney, expression of Fmo1, 3 and 5 peaks at 3 or 5 weeks of age, but in the brain, Fmo1 expression is greatest in newborns. In the kidney, FMO5 mRNA abundance is fourfold greater in males than in females, at all stages of development. Our results demonstrate that Fmo1, 2, 3, 4 and 5 exhibit distinct cell-, tissue-, sex- and developmental stage-specific patterns of expression.

Animals↗

Organization and evolution of the flavin-containing monooxygenase genes of human and mouse: identification of novel gene and pseudogene clusters.

OBJECTIVES: To date, six flavin-containing monooxygenase (FMO) genes have been identified in humans, FMOs 1, 2, 3, 4 and 6, which are located within a cluster on chromosome 1, and FMO5, which is located outside the cluster. The objectives were to review and update current knowledge of the structure and expression profiles of these genes and of their mouse counterparts and to determine, via a bioinformatics approach, whether other FMO genes are present in the human and mouse genomes. RESULTS AND CONCLUSIONS: We have identified, for the first time, a mouse Fmo6 gene. In addition, we describe a novel human FMO gene cluster on chromosome 1, located 4 Mb telomeric of the original cluster. The novel cluster contains five genes, all of which exhibit characteristics of pseudogenes. We propose the names FMO 7P, 8P, 9P, 10P and 11P for these genes. We also describe a novel mouse gene cluster, located approximately 3.5 Mb distal of the original gene cluster on Chromosome 1. The novel mouse cluster contains three genes, all of which contain full-length open-reading frames and possess no obvious features characteristic of pseudogenes. One of the genes is apparently a functional orthologue of human FMO9P. We propose the names Fmo9, 12 and 13 for the novel mouse genes. Orthologues of these genes are also present in rat. Sequence comparisons and phylogenetic analyses indicate that the novel human and mouse gene clusters arose, not from duplications of the known gene cluster, but via a series of independent gene duplication events. The mammalian FMO gene family is thus more complex than previously realised.

Amino Acid Sequence↗

Trimethylaminuria and a human FMO3 mutation database.

Trimethylaminuria (TMAuria), or fish-odor syndrome, is due to defective flavin-containing monooxygenase 3 (FMO3). In the liver, this protein catalyzes the NADPH-dependent oxidative metabolism of odorous trimethylamine (TMA), derived in the gut from dietary sources, to nonodorous trimethylamine N-oxide (TMA N-oxide). Affected individuals are unable to carry out this reaction and consequently exude a fishy body odor, due to the secretion of TMA in their breath and sweat and its excretion in their urine. This leads to a variety of psychosocial problems, including disruption of schooling, clinical depression, and attempted suicide. Twelve missense, three nonsense, and one gross deletion mutation are known to cause TMAuria. FMO3 is also a drug-metabolizing enzyme and compromised activity is expected to have implications for the efficacy of drug treatment and the possibility of adverse drug reactions both in TMAuric patients and in the general population. To date eight polymorphic variants, not associated with TMAuria, have been reported. A human FMO3 mutation database was created using MuStar, a locus-specific database system for maintaining data about allelic variants and distributing these via the World Wide Web. The database currently contains 24 entries and is accessible on the World Wide Web via the URL http://human-fmo3.biochem.ucl.ac.uk/Human_FMO3. Additional entries can be submitted via the curator of the database or via a web-based form.

Alleles↗

Genetic polymorphisms of flavin-containing monooxygenase (FMO).

Mammalian flavin-containing monooxygenase (FMO) exists as six gene families and metabolizes a plethora of drugs and xenobiotics. The major FMO in adult human liver, FMO3, is responsible for trimethylamine (TMA) N-oxygenation. A number of FMO3 mutant alleles have been described and associated with a disease termed trimethylaminuria (TMAU). The TMAU patient excretes large amounts of TMA in urine and sweat. A more recent ethnically related polymorphism in expression of the major FMO in lung, FMO2, has been described. All Caucasians and Asians genotyped to date are homozygous for a CAG --> TAG amber mutation resulting in a premature stop codon and a nonfunctional protein truncated at AA 472 (wildtype FMO2 is 535 AA). This allele has been designated hFMO2*2A. Twenty-six percent of individuals of African descent and 5% of Hispanics genotyped to date carry at least one allele coding for full-length FMO2 (hFMO2*1 allele). Preliminary evidence indicates that FMO2.1 is very active toward the S-oxygenation of low MW thioureas, including the lung toxicant ethylene thiourea. Polymorphic expression of functional FMO2 in the individuals of African and Hispanic descent may markedly influence drug metabolism and/or xenobiotic toxicity in the lung.

Animals↗

Transfection of liver in vivo by biolistic particle delivery: its use in the investigation of cytochrome P450 gene regulation.

We describe the delivery of reporter gene constructs to rat liver through the use of the Helios Gene Gun system. The effectiveness of this transfection method is illustrated by describing its use for determining in vivo the role of a DNA element that regulates cytochrome P450 2B1 (CYP2B1) gene expression in response to xenobiotics. DNA was delivered to the liver of an anesthetized animal via DNA-coated gold microcarriers. The highest level of reporter gene expression was obtained about six hours posttransfection; however, at this time endogenous CYP2B1 mRNA is transiently induced by the anesthetic treatment. The optimal time for investigating expression of a reporter gene under the control of CYP2B1 regulatory elements was 24 h after transfection, by which time the inductive effect of the anesthetic had ceased. Reporter gene expression subsequently declined rapidly to a low level by 48 h. In the transfected liver the heterologous SV40 promoter was about eight-fold stronger than the minimal CYP2B1 promoter. However, when attached to the phenobarbital response element both promoters give the same fold-induction of reporter activity in response to phenobarbital.

Animals↗

Geochemical partitioning of copper, lead, and zinc in benthic, estuarine sediment profiles.

The geochemical partitioning of copper (Cu), lead (Pb), and zinc (Zn) was examined in benthic sediment profiles (0- to 20-cm depth interval) composed of relatively coarse (65-90% sand-sized particles), noncohesive, suboxic material (Eh +120 to +260 mV). Total Cu, Pb, and Zn concentrations ranged from 8.3 to 194, 16.3 to 74.8, and 30.1 to 220 mg/kg, respectively, and were related to vertical trends in sediment texture. The observed distribution coefficients describing solid-solution partitioning were in the range of 100 to 1000 L/kg. The geochemical partitioning of solid-phase Cu, Pb, and Zn between six operationally defined fractions was examined with a sequential extraction scheme. The association of Cu, Pb, and Zn with amorphous oxides, crystalline oxides, and organic matter was linearly dependent on the abundance of each respective phase. For retention by amorphous oxide minerals, the observed stoichiometry ranged from 5.2 to 23.7 mg/g for Cu, 12.8 to 21.5 mg/g for Pb, and 23.1 to 85.7 mg/g for Zn. Corresponding values for association with crystalline oxides were an order of magnitude less than those for amorphous oxides, indicating a lesser affinity of trace metals for crystalline oxides. The stoichiometric relationships describing association with organic matter ranged from 17.6 to 54.0 mg/g for Cu, 6.1 to 9.6 mg/g for Pb, and 6.4 to 16.4 mg/g for Zn. The results from this study provide an insight into processes controlling trace metal partitioning in coarse-textured, suboxic, estuarine sediments.

Copper↗