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Biomedical subjects

E M Gibby

Publications and source records attributed to E M Gibby.

11 recordsLinked to original sources

Aspirational targets for occupational health.

The new Occupational Health Strategy for Great Britain will have national aspirational targets. These will be common goals that all partners can work to, and should help to inspire local and specific targets for action. More attention needs to be paid to looking at outcomes, so that we can reduce the number of people suffering from work-related ill-health, as well as improving the health of the workforce. Both local and national targets will need evaluating, so that progress can be seen. Organisations who share their success, as well as challenges in making progress will help to spread improving practice.

Humans↗

Establishment and characterisation of three new human ovarian carcinoma cell lines and initial evaluation of their potential in experimental chemotherapy studies.

Three new human cell lines have been established from biopsy specimens of ovarian cystadenocarcinomas: line JA-1 was derived from a primary "solid" tumour from an untreated patient, whilst the other lines were derived from ascites from patients previously treated with chlorambucil plus either cyclophosphamide (TR175) or cisplatin (TR170). Their in vitro characteristics are compared with those of the established SK-OV-3 line of similar origin. Each line has a distinct morphology and expresses a unique isozyme profile and karyotype. All 4 lines have comparable population doubling times of 28-38 hr. Only 3 lines reproducibly form colonies in soft agar, but the JA-1 line, which failed to clone, readily produces xenografts in nude mice. Drug sensitivity testing, using clonogenic or growth-inhibition assays, shows that these lines express a wide range of sensitivities to cisplatin (greater than 20-fold), with the TR175 cells proving particularly sensitive, but a narrower range of sensitivity (less than or equal to 10-fold) to adriamycin. Following 6 24-hr pulsed exposures in vitro to drug concentrations between IC50 and IC90 values, significant resistance develops to adriamycin in each line tested. In contrast, with cisplatin treatment, all lines retain their original sensitivities, except for TR170 cells exposed to the highest concentration, which express cisplatin resistance.

Cell Line↗

Selective interactions of verapamil with anthraquinones in adriamycin-sensitive and -resistant murine and human tumour cell lines in vitro.

Enhancement of the cytotoxicity of adriamycin (ADR) by addition of verpamil (VPM) was selective and, in part, concentration-dependent. In an ADR-resistant murine L5178Y lymphoma subline sensitivity was improved with ADR and 1 microM VPM, whereas the cytotoxic effects of mitoxantrone or esorubicin were not affected by VPM. In human ovarian SK-OV-3 tumour cells ADR cytotoxicity was only enhanced by 6.6 microM VPM and there was no selective advantage against an ADR-resistant subline. Circumvention of ADR resistance by VPM is not a universal phenomenon, appearing least effective against sublines expressing relatively low orders of resistance, which may be those most commonly encountered clinically.

Cell Survival↗

Conjugation of 1-naphthol by human bronchus and bronchoscopy samples.

Human bronchus, in short-term explant culture, metabolized 1-naphthol to both its sulphate ester and glucuronic acid conjugates. At low concentrations of 1-naphthol (20 microM), more 1-naphthyl sulphate than 1-naphthyl-beta-D-glucuronide was formed. At similar substrate concentrations, short-term explant cultures of both bronchus without cartilage and bronchoscopy samples, which consisted largely of bronchial epithelium, formed predominantly 1-naphthyl-beta-D-glucuronide. Thus cartilage, which alone did not significantly metabolize 1-naphthol, may in some way influence the metabolism of 1-naphthol by intact bronchus. A large inter-individual variation was observed in the conjugation of 1-naphthol by cultured human bronchus. Such variations in the conjugation of chemicals may be of importance in determining individual susceptibility to chemically induced damage.

Bronchi↗

Conjugation of 1-naphthol by human colon and tumour tissue using different experimental systems.

The metabolism of 1-naphthol, a model phenolic substrate, to its glucuronic acid and sulphate ester conjugates has been studied in short-term organ cultures of normal human colon and tumour tissue, subcellular fractions of these tissues, human colonic tumour cell lines and human colonic tumour xenografts. Normal colonic tissue, in short-term organ culture, formed more 1-naphthyl sulphate than glucuronic acid conjugates. In contrast the colonic tumours, under the same conditions, produced more 1-naphthyl beta-D-glucuronide than 1-naphthyl sulphate. A marked interindividual variation in sulphate ester and glucuronic acid conjugation was noted in both normal and tumorous colon. The conjugation of 1-naphthol was also investigated, using subcellular fractions, where the metabolism found with normal colon reflected that observed utilizing short-term organ culture, but that from colonic tumour samples did not. Cell lines derived from human colonic adenocarcinomas metabolised 1-naphthol almost exclusively to its glucuronic acid conjugate. Xenografts derived from human colonic tumours formed similar conjugates to surgical samples in culture. Thus somewhat different results were obtained dependent on the experimental model chosen. However, in all colonic tumour systems studied, when the cells remained intact and where tissue architecture was maintained, 1-naphthol was metabolised predominantly to its glucuronic acid conjugate.

Animals↗

Metabolism of benzo(a)pyrene and 1-naphthol in cultured human tumorous and nontumorous colon.

The oxidative metabolism of benzo(a)pyrene and the conjugative metabolism of 1-naphthol by explant cultures of normal human colon and colonic tumor tissue, obtained at surgery, have been studied. After 24 hr in culture, the explants were exposed to either [1-14C]-1-naphthol (20 to 100 microM) or [3H]-benzo(a) pyrene (1.5 microM) for a further 1.5 to 24 hr. Both normal-appearing tissue and tumor tissue metabolized benzo(a)pyrene to a wide variety of organic solvent-soluble metabolites, including monohydroxybenzo(a)pyrenes, dihydrodiols, and tetrols. 1-Naphthol was metabolized by cultured human colonic mucosa and tumor tissue to both its glucuronic acid and sulfate ester conjugates. In the normal tissues, with naphthol (20 microM), sulfate ester conjugation predominated. However, with the tumor tissue, sulfate ester conjugation decreased; thus, the percentage of glucuronic acid conjugates, expressed as a percentage of total metabolites formed, was increased significantly compared to normal tissue. The relationship, if any, of these changes to neoplastic transformation is unclear. The technique of explant culture described in this study may be of use for the study of other facets of the pathobiology of solid tumors.

Adenocarcinoma↗