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M Peel

Publications and source records attributed to M Peel.

At least 19 recordsLinked to original sources
PubMed2000

New aspects in genotoxic risk assessment of styrene exposure--a working hypothesis.

Styrene is one of the most important plastic monomers worldwide. Styrene-7,8-oxide (SO), the major in-vivo metabolite of styrene, is classified as probably carcinogenic to humans and carcinogenic in rodents. Biological monitoring of exposure to styrene is usually carried out by determination of mandelic acid and phenylglyoxylic acid, the two main styrene metabolites in urine. SO binds covalently to human plasma protein and haemoglobin. The ability of SO to induce DNA adducts and DNA strand-breaks has been well documented. Recently in-vitro results showed that SO may disrupt the pre-existing oxidative status in white blood cells. This disruption would alter the balance between oxidants and antioxidants in cells. Styrene exposure can also result in oxidative DNA damage. A significant increase of 8-hydroxy-2;-deoxyguanosine (8-OHdG) has been found in white blood cells of styrene-exposed workers. According to these findings we propose a new hypothesis for the genotoxic risk assessment of styrene. Depletion of glutathione and increase in lipid peroxidation, similarity in the decrease of high molecular weight (HMW) DNA fragments after SO exposure compared to hydrogen peroxide (H(2)O(2)) exposure, oxidative DNA damage (increased amounts of 8-OHdG and an increased level of DNA strand-breaks) following styrene or SO exposure are due to oxidative stress which can be a result of the imbalance between oxidants and antioxidants. Formation of protein-, RNA- and DNA-adducts, changes in DNA repair capacity and styrene metabolism following styrene exposure could cause this imbalance between oxidants and antioxidants. Oxidative stress seems to be the basis for genotoxic risk assessment of styrene.

Humans↗
PubMed1998

Structures of homologous composite transposons carrying cbaABC genes from Europe and North America.

IS1071 is a class II transposable element carrying a tnpA gene related to the transposase genes of the Tn3 family. Copies of IS1071 that are conserved with more than 99% nucleotide sequence identity have been found as direct repeats flanking a remarkable variety of catabolic gene sequences worldwide. The sequences of chlorobenzoate catabolic transposons found on pBRC60 (Tn5271) in Niagara Falls, N.Y., and on pCPE3 in Bologna, Italy, show that these transposons were formed from highly homologous IS1071 and cbaABC components (levels of identity, > 99.5 and > 99.3%, respectively). Nevertheless, the junction sequences between the IS1071L and IS1071R elements and the internal DNA differ by 41 and 927 bp, respectively, suggesting that these transposons were assembled independently on the two plasmids. The formation of the right junction in both transposons truncated an open reading frame for a putative aryl-coenzyme A ligase with sequence similarity to benzoate- and p-hydroxybenzoate-coenzyme A ligases of Rhodopseudomonas palustris.

Alcaligenes↗
PubMed1997

Comparison of the binding potential of various diisocyanates on DNA in vitro.

Inhalation of diisocyanate vapors is associated with immediate-type hypersensitivity reactions and direct toxic responses. The genotoxic effects of diisocyanates have not been clarified. The aim of this study was to examine the changes in DNA following in vitro exposure to three most commonly used diisocyanates (toluene diisocyanate, TDI; methylenediphenyl-4,4'-diisocyanate, MDI; and hexamethylene diisocyanate, HDI) and to compare their binding potential using melting behavior of DNA and electrophoresis studies in DNA. Following incubation of DNA with MDI (pure and mix) and HDI we found no differences in the melting behavior compared to the control calf thymus DNA. However, DNA treated with TDI showed differences in the shape of the native DNA curves due to changes in hyperchromicity and exhibited 14% more DNA reconstitution after renaturation. The small changes in the melting behavior of native DNA do not suggest the formation of DNA intrastrand cross-links but rather conformational changes of single- and double-stranded DNA. These conformational changes were further explored by agarose electrophoresis of native and denatured calf thymus DNA. Control and all diisocyanate-exposed DNA showed no differences in the size of native DNA fragments. Conversely, electrophoresis of TDI mix-incubated DNA, following denaturation, showed a distinct reduction in the double-stranded DNA fragment size compared to the control, MDI-denatured (pure and mix), and HDI-denatured DNA. These findings may help to better understand the mechanisms of the genotoxic effect of TDI.

Animals↗
PubMed1997

Hunger strikes.

Explore the source record for details and available documents.

Food Deprivation↗
PubMed1997

Changes in high molecular weight DNA fragmentation following human blood exposure to styrene-7,8-oxide.

Styrene-7,8-oxide (S7,8O) is the major in vivo metabolite of styrene and is a genotoxic agent potentially carcinogenic to humans. It is known to cause DNA strand breaks and adducts. We studied high molecular weight DNA fragmentation in white blood cells following incubation of blood with S7,8O from individuals with no previous exposure to this compound. To better understand the effects of S7,8O, we also examined blood exposed to hydrogen peroxide (H2O2) a typical oxidant that is linked to oxidative stress. All individuals in this study showed a variable reduction in high molecular weight DNA fragments determined by laser densitometry compared to untreated controls for both S7,8O and H2O2 treated samples. This decrease was independent of the concentration and length of exposure of blood to S7,8O and H2O2. An increase in low molecular weight DNA fragments from samples treated with S7,8O and H2O2, compared to untreated samples was also noted. Similarities in the reduction of HMW-DNA fragments after S7,8O and H2O2 exposure suggested a similar mechanism of HMW-DNA damage. It was surmised that S7,8O exposure in blood may induce high molecular weight DNA fragmentation due to oxidative stress.

Carcinogens↗
PubMed1995

Synthesis and antitumor activity of novel water soluble derivatives of camptothecin as specific inhibitors of topoisomerase I.

The synthesis and antitumor activities of the novel water soluble camptothecin derivatives 7-[(4-methylpiperazino)methyl]-10,11-(methylenedioxy)-(20S)-campto thecin trifluoroacetate (6) and 7-[(4-methylpiperazino)methyl]-10,11-(ethylenedioxy)-(20S)-camptot hecin trifluoroacetate (7) are described. The solubilities of compounds 6 and 7 were measured to be 4.5 and 5.8 mg/mL, respectively, in pH 5 acetate buffer in contrast to < 0.003 mg/mL for camptothecin in the same buffer. In the purified topoisomerase I cleavable complex enzyme assay, compounds 6 and 7 demonstrated potent inhibition of topoisomerase I with IC50's of 300 and 416 nM, respectively, in comparison to 679 nM for camptothecin and 1028 nM for topotecan. In human tumor cell cytotoxicity assays, compounds 6 and 7 demonstrated potent antitumor activity against ovarian (SKOV3), ovarian with upregulated MDRp-glycoprotein (SKVLB), melanoma (LOX), breast (T47D), and colon (HT29) with IC50's ranging from 0.5 to 102 nM. Compounds 6 and 7 induced tumor regressions in the HT29 human colon tumor xenograft model and demonstrated similar rank order of potency compared to in vitro assay results.

Animals↗
PubMed1995

The occupational health of de-miners in Afghanistan.

In the last few years there has been increasing awareness of the problems of landmines. This has focused on the ethics of landmine use, and the dangers to the local population of minefields. It has culminated in a much needed campaign for a moratorium on landmine manufacture. There are, however, millions of mines left in almost all parts of the world, which can create an indefinite hazard. The only solution is the slow and painstaking task of clearing these minefields. The health and safety of de-miners has not been previously discussed in any detail. This paper addresses the hazards to the people clearing minefields, with specific reference to the activities of the HALO trust in Afghanistan. De-miners are subject to the same hazards from mines as the general population, but put themselves at additional risk by entering minefields deliberately. These hazards can be controlled by a safe system of work and the appropriate use of personal protective equipment.

Accident Prevention↗
PubMed1994

Distribution of the catabolic transposon Tn5271 in a groundwater bioremediation system.

The distribution of Tn5271-related DNA sequences in samples of groundwater and a groundwater bioremediation system at the Hyde Park (Niagara Falls, N.Y.) chemical landfill site was investigated. PCR amplification of target sequences within the cha genes of Tn5271 revealed similar sequences in the groundwater community and in samples from the sequencing batch reactors treating that groundwater. Cell dilution combined with PCR amplification indicated that cha sequences were carried in about 1 of 10 culturable bacteria from the treatment system. Characterization of isolates involved in chlorobenzoate and toluene biodegradation in the treatment system indicated that two phenotypic clusters, Alcaligenes faecalis type 2 and CDC group IVC-2, contained all of the Tn5271 probe-positive isolates from the community. These two groups differed phenotypically from recipient groups isolated following horizontal transfer of pBRC60 (Tn5271) in pristine freshwater microcosms. A genetic rearrangement in Tn5271 attributable to the intramolecular transposition of the flanking element IS1071R was detected in an isolate from the treatment system. Comparison of the structure of the intramolecular transposition derivative from groundwater isolate OCC13(pBRC13) with a laboratory-derived intramolecular transposition derivative of pBRC60 revealed similarities. The rearrangement was shown to increase the stability of the plasmid under starvation conditions.

Alcaligenes↗
PubMed1988

Temperature-dependent expression of flagella of Listeria monocytogenes studied by electron microscopy, SDS-PAGE and western blotting.

Washed cells of Listeria monocytogenes serotype 4b, grown in broth culture at 20 degrees C and at 37 degrees C, were examined by electron microscopy for the presence of flagella. Many flagella were seen in cells grown at 20 degrees C, whereas at 37 degrees C very few were expressed. Flagella sheared from the cell surface were partially purified by differential centrifugation. Using SDS-PAGE and Western blotting two distinct protein bands were seen in this preparation, both with an apparent molecular mass of approximately 29 kDa. Further purification of these proteins was achieved by gel filtration and ion-exchange chromatography. Whole organisms grown at 20 degrees C and 37 degrees C were examined in Western blots using an affinity-purified polyclonal antibody, and a monoclonal antibody, both directed against 29 kDa putative flagellin. Bacteria grown at 20 degrees C expressed abundant flagellin, whereas only trace amounts could be detected in organisms grown at 37 degrees C. It is concluded that organisms grown at 20 degrees C both produce and assemble flagellin at the cell surface, and that flagellin production is a less marked feature of organisms grown at 37 degrees C.

Blotting, Western↗
PubMed1988

Physical and antigenic heterogeneity in the flagellins of Listeria monocytogenes and L. ivanovii.

Listeria monocytogenes serotypes 4a, 4b and 7, and L. ivanovii, all grown at 20 degrees C, were negatively stained and examined by electron microscopy. Crude extracts of the cell surface of L. monocytogenes serotypes 1/2b, 3b, 3c, 4a, 4b, 4d and 7 and of L. ivanovii (all grown at 20 degrees C) were examined by SDS-PAGE and Western blotting using (i) affinity-purified polyclonal monospecific antibody, and (ii) monoclonal antibody, each raised against 29 kDa flagellin of serotype 4b. No flagella were seen on serotype 7 by electron microscopy and no flagellin was detected in crude cell surface extracts of serotype 7 either in silver-stained gels or in Western blots. The monospecific polyclonal antibody detected flagellins of approximate molecular mass 29 kDa in each of the seven flagellate strains including L. ivanovii. The monoclonal antibody detected 29 kDa flagellin in serotypes 1/2b, 3b, 4a, 4b and 4d, but not the flagellins of serotype 3c or L. ivanovii, which had a slightly lower molecular mass. Following prolonged electrophoresis of crude flagellar extracts the 29 kDa complex was resolved into three closely migrating bands. In a heterologous system using serotype 1/2b crude flagellar extract, all three bands were detected using the polyclonal antibody whereas only two bands were detected by the monoclonal antibody. It is concluded that polyclonal anti-flagellin antibodies are not useful tools with which to distinguish serotypes of L. monocytogenes sensu lato in immunoblotting, but that differences can be determined using a monoclonal antibody directed against particular components of the flagellar complex. These differences did not fully correspond to those anticipated from results of agglutination tests.

Antigens, Bacterial↗