James R Whiteside

Publications (4)7.37 Total impact

• Article: Timeframes of UVA-induced bystander effects in human keratinocytes.

  James R Whiteside, Sarah L Allinson, Trevor J McMillan
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  ABSTRACT: The bystander effect is defined as the induction of cellular damage in unirradiated cells, induced by irradiated cells in the surrounding area. Our laboratory has previously identified that an environmentally relevant dose of UVA is able to induce the effect in human keratinocytes and fibroblasts, seen as reduced clonogenic survival. Here we report on our investigations into the periods over which the bystander signals are released by the irradiated cells and for how long unirradiated cells need to be exposed to them for the effect to be induced. Using a coincubation system we have identified that irradiated cells do not release the signals immediately following irradiation but have a time lag of over 24 h before levels are sufficient to induce the effect, with the signals being released for a minimum of 3 days following irradiation. We have also found that the recipient cells only require at most 24 h of exposure to these signals for induction of the effect. These data indicate that a single exposure to UVA can exert an effect for several days postirradiation, thus amplifying the deleterious effects of exposure.
  Photochemistry and Photobiology 12/2010; 87(2):435-40. · 2.41 Impact Factor
• Article: Cellular and sub-cellular responses to UVA in relation to carcinogenesis.

  Andrew J Ridley, James R Whiteside, Trevor J McMillan, Sarah L Allinson
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  ABSTRACT: UVA radiation (315-400 nm) contributes to skin aging and carcinogenesis. The aim of this review is to consider the mechanisms that underlie UVA-induced cellular damage, how this damage may be prevented or repaired and the signal transduction processes that are elicited in response to it. Exposure to ultraviolet (UV) light is well-established as the causative factor in skin cancer. Until recently, most work on the mechanisms that underlie skin carcinogenesis focused on shorter wavelength UVB radiation (280-315 nm), however in recent years there has been increased interest in the contribution made by UVA. UVA is able to cause a range of damage to cellular biomolecules including lipid peroxidation, oxidized protein and DNA damage, such as 8-oxoguanine and cyclobutane pyrimidine dimers. Such damage is strongly implicated in both cell death and malignant transformation and cells have a number of mechanisms in place to mitigate the effects of UVA exposure, including antioxidants, DNA repair, and stress signalling pathways. The past decade has seen a surge of interest in the biological effects of UVA exposure as its significance to the process of photo-carcinogenesis has become increasingly evident. However, unpicking the unique complexity of the cellular response to UVA, which is only now becoming apparent, will be a major challenge for the field of photobiology in the 21st century.
  International Journal of Radiation Biology 04/2009; 85(3):177-95. · 2.28 Impact Factor
• Article: A bystander effect is induced in human cells treated with UVA radiation but not UVB radiation.

  James R Whiteside, Trevor J McMillan
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  ABSTRACT: The bystander effect is defined as the induction of damage in nonirradiated cells by irradiated cells. The significance on health is unknown, but the effective amplification of deleterious effects of cytotoxic agents is a concern. In this study the ability of UVA or UVB radiation to induce the bystander effect in human keratinocytes (HaCaT) and fibroblasts (MRC5) was examined using a method that involved the co-incubation of two differentially treated cell populations separated by a medium-permeable insert. This allowed the study of interactions between cells in the absence of direct cell-to-cell contact. Irradiation of one population with 100 kJ/m(2) UVA radiation induced a bystander effect in a second population of unirradiated cells that was manifested as reduced clonogenic survival. This effect was induced within and between the two cell lines but was not seen after treatment with 400 J/m(2) UVB radiation. An additional reduction in survival above that expected to occur as a result of direct exposure was observed when the two UVA-irradiated populations were co-incubated. As well as providing some potentially important information regarding the biological effects of UV light, the spectral variation in the induction of the effect provides a useful approach to dissecting the mechanisms underlying such effects.
  Radiation Research 03/2009; 171(2):204-11. · 2.68 Impact Factor
• Article: Cadmium and copper inhibit both DNA repair activities of polynucleotide kinase

  James R. Whiteside, Clare L. Box, Trevor J. McMillan, Sarah L. Allinson
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  ABSTRACT: Human exposure to heavy metals is of increasing concern due to their well-documented toxicological and carcinogenic effects and rising environmental levels through industrial processes and pollution. It has been widely reported that such metals can be genotoxic by several modes of action including generation of reactive oxygen species and inhibition of DNA repair. However, although it has been observed that certain heavy metals can inhibit single strand break (SSB) rejoining, the effects of these metals on SSB end-processing enzymes has not previously been investigated. Accordingly, we have investigated the potential inhibition of polynucleotide kinase (PNK)-dependent single strand break repair by six metals: cadmium, cobalt, copper, nickel, lead and zinc. It was found that micromolar concentrations of cadmium and copper are able to inhibit the phosphatase and kinase activities of PNK in both human cell extracts and purified recombinant protein, while the other metals had no effect at the concentrations tested. The inhibition of PNK by environmentally and physiologically relevant concentrations of cadmium and copper suggests a novel means by which these toxic heavy metals may exert their carcinogenic and neurotoxic effects.
  DNA Repair.