Longitudinal variation in O6-alkylguanine DNA-alkyltransferase activity in the human colon and rectum

In a systematic study of O6-alkylguanine DNA-alkyltransferase activity in the human colon and rectum, tumours were found to occur in regions of low activity. These results are consistent with the hypothesis that O6-alkylguanine DNA-alkyltransferase levels and alkylating agent exposure may be important determinants of large bowel tumorigenesis

The Influence of Sequence Variability and Dimerization on Mannose Binding in Monocot Mannose Binding Lectins

Abstract Motivation. A model of the lectin from Aloe arborescens was built by homology modeling. Docking studies with mannose were performed on this model and the known crystal structures of monocot mannose binding lectins from snowdrop and garlic. On the basis of these results association of monomers to form dimers is found to be necessary for successful binding of mannose by site III of these lectins, by providing the fourth strand of the -sheet that is a supporting edge for the site. From an analysis of the carbohydrate binding sites (I, II and III) of the above lectins and the docking studies, the mannose binding site I of aloe lectin is predicted to retain the ability to bind mannose with all of the key residues involved in binding unchanged. Site II and III lose residues specific for hydrogen bonding and are predicted to be unable to bind mannose. Aloe lectin monomers are shown to be able to associate as dimers but docking is still unsuccessful in site III. Method. Protein homology modeling and AutoDock docking studies were used in this study. Results. A homology model of aloe lectin was created by both manual and automatic methods and its ability to bind the natural substrate mannose was assessed by docking studies using the genetic algorithm approach in the AutoDock program. The results of the docking studies were correlated with those on lectins for which X-ray crystal data is known and rationalized in terms of specific mutations in the aloe lectin binding sites. Conclusions. Aloe lectin is predicted to be able to bind mannose in its site I binding site, unable to bind in site II because of key residue mutations and also unable to bind in site III

Fern spore extracts can damage DNA

The carcinogenicity of the vegetative tissues of bracken fern (Pteridium) has long been established. More recently, the carcinogenic effects of the spores of bracken have also been recognized. Both vegetative tissues and spores of bracken can induce adducts in DNA in animal tissues, but the possible genotoxic or carcinogenic effects of spores from fern species other than bracken are unknown. The single-cell gel electrophoresis (‘comet’) assay was used to investigate whether fern spores can cause DNA damage in vitro. Extracts of spores from six fern species were administered to cultured human premyeloid leukaemia (K562) cells. Spore extracts of five fern species: Anemia phyllitidis, Dicksonia antarctica, Pteridium aquilinum, Pteris vittata and Sadleria pallida, induced significantly more DNA strand breaks than those in the control groups. Only in one species, Osmunda regalis, was the effect no different from that in the control groups. Using extracts from A. phyllitidis and P. vittata, the extent of DNA damage was increased by increasing the original dose 10 times, whereas an experiment in which exposure times were varied suggested that the highest levels of strand breaks appear after 2 h exposure. Simultaneous incubation with human S9 liver enzyme mix ablated the damaging effect of the extracts. Our data show that fern spore extracts can cause DNA damage in human cells in vitro. Considering the strong correlation between DNA damage and carcinogenic events, the observations made in this report may well have some implications for human health. © 2000 Cancer Research Campaig

Geochemical compositional controls on DNA strand breaks induced in in vitro cell-free assays by crushed rock powders from the Panasqueira mine area, Portugal

From Springer Nature via Jisc Publications RouterHistory: received 2019-12-15, accepted 2020-06-24, registration 2020-06-24, pub-electronic 2020-07-09, online 2020-07-09, pub-print 2021-07Publication status: PublishedFunder: Saudi Arabia Cultural Bureau in London; doi: http://dx.doi.org/10.13039/100012363Abstract: DNA strand breaks are a common form of DNA damage that can contribute to chromosomal instability or gene mutations. Such strand breaks may be caused by exposure to heavy metals. The aim of this study was to assess the level of DNA strand breaks caused by µm-scale solid particles of known chemical composition with elevated heavy metals/metalloids, notably arsenic, using an in vitro cell-free DNA plasmid scission assay. These samples were incubated with and without H2O2 to see whether damage occurs directly or indirectly through the Fenton reaction. Levels of DNA damage in the absence of H2O2 were < 10%, but in the presence of H2O2, all samples showed higher levels of damage ranging from 10 to 100% suggesting that damage was being incurred through the Fenton reaction. Using bivariate correlation analysis and multiple linear regression, manganese oxide (MnO), sulphur (S), copper (Cu), and zinc (Zn) concentrations in the particulates were found to be the most significant predictors of DNA damage. The mechanism of this DNA damage formation has yet to be thoroughly investigated but is hypothesised to be due to reactive oxygen species formation. Further work is required to assess the extent of contribution of reactive oxygen species to this DNA damage, but this study highlights the potential role of chemistry and/or mineralogy to the extent and/or nature of DNA damage caused by particulates

The application of ultrasonic NDT techniques in tribology

The use of ultrasonic reflection is emerging as a technique for studying tribological contacts. Ultrasonic waves can be transmitted non-destructively through machine components and their behaviour at an interface describes the characteristics of that contact. This paper is a review of the current state of understanding of the mechanisms of ultrasonic reflection at interfaces, and how this has been used to investigate the processes of dry rough surface contact and lubricated contact. The review extends to cover how ultrasound has been used to study the tribological function of certain engineering machine elements