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S Neale

Publications and source records attributed to S Neale.

28 records · Page 2Linked to original sources

Physiological modification of alkylating-agent induced mutagenesis. I. Effect of growth rate and repair capacity on nitrosomethylurea-induced mutation of Escharichia coli.

The effects of repair capacity and growth rate on the induction of mutations by N-methyl-N-nitosourea (MNUA) was investigated using the trpE reversion system of Escherichia coli WP2 and some repair-deficient derivatives isogenic for this gene. In all these strains reducing the growth rate prior to MNUA-treatment caused a reduction in the mutational response, however major differences were observed between strains. In exrA and recA- bacteria stationary phase cells were 100 times less mutable than cells grown at a mean generation time (m.g.t.) of 30 min, whereas reductions of 12 and 25 times were observed in the uvrA- and wild-type strains respectively. In contrast the mutational response of the polA- mutant varied only slightly with growth rate; the increases at high MNUA concentrations being equal to the increase in the trpE gene number. These results show the increasing importance of the error-prone exrA+/recA+-dependent repair system in mutation-induction by MNUA as the growth rate of the culture is reduced and its relative unimportance for mutation induction in nutrient broth-grown cells (m.g.t. 30 min).

Cell Division↗

Physiological modification of alkylating agent induced mutagenesis. II. Influence of the numbers of chromosome replicating forks and gene copies on the frequency of mutations induced in Escherichia coli.

The frequency of reversions induced in Escherichia coli K-12 trpA58 by any of five different monofunctional alkylating agents increased as the growth rate of the organism was raised prior to mutagen treatment. The increase in mutation frequency did not correlate with growth rate-dependent changes in cell area or total cellular protein and DNA. After treatment of cells with N-methyl-N-nitrosourea (MNUA), no growth rate-dependent change was observed in the total DNA alkylation or percentage of O6-methylguanine present in the DNA extracted. The frequency of reversions induced by one mutagen, methyl methanesulphonate (MMS), increased in proportion to the average number of trpA gene copies per cell, whereas the frequency of reversions induced by the other compounds was dependent on the average number of chromosome replicating forks per cell. This difference was attributed to the different ratios of DNA base alkylation products observed, formed after treatment with MMS, an SN2-type reagent, or after treatment with the SN1-type reagents ethyl methanesulphonate (EMS), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), MNUA and N-ethyl-N-nitrosourea (ENUA). Possible reasons for the dependence of mutation frequency on the number of replicating forks per cell are discussed.

Alkylating Agents↗

The effect of isoprenaline on induction of tumours by methyl nitrosourea in the salivary and mammary glands of female wistar rats.

Pretreatment of rats with isoprenaline sulphate (IPR) stimulated DNA synthesis in both salivary and mammary gland tissues. Salivary gland tumours induced by N-methyl-N-nitrosourea (MNU) were observed for the first time in rats, but occurred only in IPR-pretreated animals given MNU during the period of IPR-stimulated DNA synthesis. The cumulative index of MNU-induced mammary tumours and the number of tumours per tumour-bearing rat were increased by IPR-pretreament only if the animals received MNU during the period of IPR-stimulated DNA synthesis.

Animals↗

Cell cytometry with a light touch: sorting microscopic matter with an optical lattice.

Lab-on-a-chip design is a key technology for increasing both the reliability and the functionality of many different preparation and diagnostic techniques in biomedicine. The drive towards ever more integrated lab-on-a-chip designs requires increasingly complex microfluidic systems. In order to build these systems, non-invasive actuators such as pumps, filters and mixers are required. We have demonstrated microfluidic sorting based on a 3D interference pattern, formed from multiple coherent laser beams, which has the potential to fulfil all the above criteria. By interfering five laser beams from a fibre laser at 1070 nm, we have formed a 3D optical lattice. When particles flow through the optical lattice their trajectories depend upon the force exerted on the particle by the optical lattice, in combination with the drag force exerted by the fluid flow. Hence, with the strength of a particle's interaction with the lattice determining the total force exerted upon it, its trajectory is determined by its physical properties. These properties include refractive index, size and shape, giving a range of criteria with which to sort an analyte. We have shown separation at 45 degrees of polymer from silica microspheres (by refractive index), the separation of protein microcapsules and the sorting of erythrocytes from lymphocytes. The interference pattern can be tailored to the particles and if a blockage occurs, the laser can simply be switched off, unlike solid-state micro-sorters, so that no jamming occurs. Efficiencies in excess of 95% have been achieved.

Animals↗