21 research outputs found

    Sulphate ester and glucuronic acid conjugation reactions of normal and tumour tissues using different experimental systems.

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    Sulphate ester and glucuronic acid conjugations are major pathways of Phase 2 drug metabolism. Their comparative study, in normal and tumour tissues, was undertaken, using various in vitro systems. The major xenobiotic used was 1-naphthol, its conjugation by UDP-glucuronosyl-transferase and sulphotransferase to 1-naphthyl-beta-D-glucuronide and 1-naphthyl sulphate respectively, being investigated. Normal human lung and colon tissue in short-term organ culture formed more 1-naphthyl sulphate, whereas tumours from these organs produced more 1-naphthyl-beta-D-glucuronide, there being a change in conjugation pathways from normal to tumour tissue. Such biochemical differences in human tissues could be exploitable in cancer chemotherapy. Possible reasons for this shift in metabolism include: changes in enzyme protein; availability of cofactors; alterations in hydrolysing enzymes. It may even be connected to alterations in cell-surface glycosaminoglycans. Normal peripheral human lung in organ culture formed almost exclusively 1-naphthyl sulphate, whereas tumour tissue from squamous carcinomas gave predominantly 1-naphthyl-beta-D-glucuronide. Normal colon produced a different pattern of conjugation from colorectal tumours. Subcellular fractions, from lung specimens, reflected the metabolism seen in culture, while those from colonic samples did not. Human bronchial carcinoma cell lines, but not those from human colon adenocarcinomas, generally produced a conjugation pattern suggesting a reasonable model for surgical tumour samples in culture. Xenografts derived from human lung and colon tumours gave a similar conjugation pattern as surgical samples in culture. Species differences occurred with short-term organ cultures from normal rodent lung and colon tissues, which produced conjugation patterns unlike those obtained from normal human tissues. For these pathways, rodent tissues would provide unsatisfactory models for humans. These results emphasised the difficulties in extrapolating from animal data to man and the importance of studying human tissues. Thus, using organ culture of human tissue, improved understanding of human metabolism, target organ toxicity and individualising treatment by testing chemosensitivity of drugs may be obtained

    Sulphate ester and glucuronic acid conjugation reactions of normal and tumour tissues using different experimental systems.

    No full text
    Sulphate ester and glucuronic acid conjugations are major pathways of Phase 2 drug metabolism. Their comparative study, in normal and tumour tissues, was undertaken, using various in vitro systems. The major xenobiotic used was 1-naphthol, its conjugation by UDP-glucuronosyl-transferase and sulphotransferase to 1-naphthyl-beta-D-glucuronide and 1-naphthyl sulphate respectively, being investigated. Normal human lung and colon tissue in short-term organ culture formed more 1-naphthyl sulphate, whereas tumours from these organs produced more 1-naphthyl-beta-D-glucuronide, there being a change in conjugation pathways from normal to tumour tissue. Such biochemical differences in human tissues could be exploitable in cancer chemotherapy. Possible reasons for this shift in metabolism include: changes in enzyme protein; availability of cofactors; alterations in hydrolysing enzymes. It may even be connected to alterations in cell-surface glycosaminoglycans. Normal peripheral human lung in organ culture formed almost exclusively 1-naphthyl sulphate, whereas tumour tissue from squamous carcinomas gave predominantly 1-naphthyl-beta-D-glucuronide. Normal colon produced a different pattern of conjugation from colorectal tumours. Subcellular fractions, from lung specimens, reflected the metabolism seen in culture, while those from colonic samples did not. Human bronchial carcinoma cell lines, but not those from human colon adenocarcinomas, generally produced a conjugation pattern suggesting a reasonable model for surgical tumour samples in culture. Xenografts derived from human lung and colon tumours gave a similar conjugation pattern as surgical samples in culture. Species differences occurred with short-term organ cultures from normal rodent lung and colon tissues, which produced conjugation patterns unlike those obtained from normal human tissues. For these pathways, rodent tissues would provide unsatisfactory models for humans. These results emphasised the difficulties in extrapolating from animal data to man and the importance of studying human tissues. Thus, using organ culture of human tissue, improved understanding of human metabolism, target organ toxicity and individualising treatment by testing chemosensitivity of drugs may be obtained

    Hybrid zones in Rhododendron subsection Taliensia

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    The investigation of hybrid zones has proven to be one of the most promising approaches to advance our understanding of species barriers, and to elucidate evolutionary processes involved in speciation. Due to the improvement of molecular techniques it will soon be possible to investigate the genetic composition of non-model species in much greater detail, and also include species that defy investigation using controlled laboratory conditions. To be able to draw further reaching conclusions about the generality of certain evolutionary factors, it is crucial to investigate a wide spectrum of organisms differing in traits, life histories and relatedness. This study investigates patterns of hybridisation between two pairs of closely related species in the genus Rhododendron. AFLP data for 346 loci, from twelve populations in total comprising 390 individuals, were obtained. Additionally, the abundance of three alkane components in the leaf waxes of 115 individuals was determined. For the species pair R. clementinae and R. roxieanum low levels of recent hybridisation were found, however, the wax composition of R. roxieanum var. cucullatum suggests historical introgression. Two types of hybrid zones were found for R. aganniphum and R. phaeochrysum, one mainly comprising F1 individuals, and the other frequent backcrosses to R. aganniphum. Furthermore, evidence for genomic incompatibilities at several loci for the two species will be presented, and hybrid identity of R. aganniphum var. avorufum and R. phaeochrysum var. agglutinatum is suggested.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
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