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Title: Biological sensitizers of near UV : generation of reactive oxygen species and damage to cellular components and microbes
Author: Hargreaves, Aspasia
ISNI:       0000 0001 2416 6724
Awarding Body: Nottingham Trent University
Current Institution: Nottingham Trent University
Date of Award: 2001
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Most of the harmful effects of the near ultraviolet (NUV) radiation (290-400 nm) on living organisms appear to be mediated via activation of molecular sensitisers. Thus, the potential of L-histidine, L(+)mandelic acid, β-phenylpyruvic acid, p-OH-phenylpyruvic acid and L-β-phenyllactic acid to be photolysed by NUV and affect biological systems was investigated. An interest for these compounds was expressed, since they are ubiquitous components of living organisms and, in particular, a part of the metabolic pathway of phenylalanine in humans. On NUV exposure, these endogenous biochemicals are proposed to react with molecular oxygen in aqueous solution to generate a variety of reactive oxygen species (ROS) such as H₂O₂ , OH, O₂ / HO , and ¹O₂ Chemical assays and the use of selective scavengers aided in the identification of such ROS and have elucidated some possible mechanistic pathways for ROS generation. ROS production on NUV photolysis of L-histidine, L(+)mandelic acid and p-OH-phenylpyruvic acid was found to be pH-dependent and maximal in alkaline media, whereas β-phenylpyruvic acid appeared most susceptible to photolysis to produce ROS at near physiological pH (pH 7-7.5), an effect that renders it great biological importance. For this reason, the biological effects of photosensitised reactions of β-phenylpyruvic acid were studied in a greater detail than that of other sensitisers. The NUV photolysis of L-histidine, L(+)mandelic acid, β-phenylpyruvic acid and p-OH-phenylpyruvic acid was shown to cause synergistic inactivation of bacteriophage T7, in a dose and pH dependent manner. β-Phenylpyruvic acid was also shown to cause lethality in bacteria, with gram-positive cells being more susceptible than gram-negatives to sensitised NUV inactivation. Subsequently, using HPLC, the cellular concentrations and incorporation of β-phenylpyruvic acid in bacteria were determined. An assessment of the effect of NUV plus sensitisers (β-phenylpyruvic acid in particular) on individual cellular components such as DNA, lipids and proteins revealed that the photosensitised action of these compounds can cause oxidative damage to all these biomolecules. Thus, the NUV photolysis of β-phenylpyruvic acid was responsible for a variety of DNA damage such as formation of single-strand breaks to pBR322 that subsequently increased its transformation efficiency, DNA damage-induced production of β-galactosidase, and induction of mutations resulting in antibiotic resistance. The NUV photolysis of this compound also resulted in lipid peroxidation of liposomes and bacterial cells and protein damage such as fragmentation of BSA and oxidative modification of E. coli proteins. It is therefore possible that L-histidine, L(+)mandelic acid, β-phenylpyruvic acid, p-OH-phenylpyruvic acid and L-β-phenyllactic acid may contribute, in different extends, to some of the effects of solar radiation on health, such as photoageing and ocular damage.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Photosensitizers; Photoageing; Human