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Biomedical subjects

S M Edwards

Publications and source records attributed to S M Edwards.

11 recordsLinked to original sources
PubMed1995

Cytotoxic and clastogenic effects of benzyl isothiocyanate towards cultured mammalian cells.

Benzyl isothiocyanate (BITC), a compound found in cruciferous vegetables present in the human diet, has previously been shown to induce chromosome aberrations in an Indian muntjac cell line. The results of this study show that it also induces both chromosome aberrations and sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells in the absence of an exogenous metabolic activation system and induces DNA strand breaks as measured by the single-cell gel electrophoresis assay. However, whereas it increased the number of aberrations four-fold, it was not able to raise SCE levels by more than 50% and there was a levelling-off in the dose-response curve. Whereas the survival curve of CHO cells exposed to BITC was linear in shape, that of the human colorectal adenocarcinoma cell line HT29 was found to fit the exponential model (with an alpha equivalent of 0.28 and a beta equivalent of 2.80, where the concentration of BITC is measured in micrograms/ml). This pattern of clastogenic and cytotoxic activities is reminiscent of that generated by ionizing radiation and certain radiomimetic chemotherapeutic agents.

Adenocarcinoma↗
PubMed1994

Quantitative in vitro assessment of phototoxicity using a human skin model, Skin2.

The ability to accurately predict the phototoxic potential of personal and skin care products remains a key element in assessing the safety of premarketed products. To find a reliable in vitro alternative test for photoirritancy, the European Commission and the European Cosmetic Association are conducting a 3-year, European validation study. Based on the results of this study, an in vitro photoirritancy method will be selected for incorporation into new international guidelines for photoirritancy testing. As a part of this study, Skin2, a cultured human skin system, was used to evaluate the phototoxic potential of chemicals with known photoirritative properties. The Skin2 ZK1351, a 3-dimensional co-culture system, consists of dermal fibroblasts and a multilayered epidermis comprising differentiated keratinocytes. This product line has previously been used to evaluate the irritative potential of topically applied ingredients and products. In this study, various concentrations of the test chemicals were applied to the epidermal side of the Skin2 tissue for contact times of 1 h or 24 h and then the tissue was exposed to 2.9 J/cm2 of ultraviolet A (UVA) radiation. Treated but nonirradiated tissues were also assayed to predict the cytotoxic potential of the test chemicals, which could mask the phototoxic reaction. After exposure, the tissue substrates were rinsed free of test chemicals and allowed to recover for 24 h. Following this incubation, the MTT reduction assay was used to assess cytotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzophenones↗
PubMed1993

Mutation induction by ionizing radiation in three human bladder tumour cell lines.

Mutation induction at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus has been studied in three human bladder tumour cell lines of varying radiosensitivity. U1-S40b, a radiosensitive mutant clone of MGH-U1, has been previously reported to show no difference in split-dose recovery or low dose-rate sparing, but to have an impaired repair fidelity when compared to its parent line. In this paper we have shown that U1-S40b is less mutable at the hprt locus at a similar level of survival. This may represent an increased incidence of severe or non-repairable lesions, making hprt- mutants poorly recoverable in U1-S40b when compared to MGH-U1. No difference was seen in mutation induction between MGH-U1 and RT112, another human bladder tumour cell line of similar radiosensitivity to MGH-U1.

Carcinoma, Transitional Cell↗
PubMed1992

A DNA repair defect in a radiation-sensitive clone of a human bladder carcinoma cell line.

DNA repair was measured in an ionising radiation-sensitive mutant of a human bladder carcinoma cell line. No difference in the rate or extent of double-strand break rejoining was found using the techniques of neutral filter elution and pulsed-field gel electrophoresis. In contrast, significant differences in repair fidelity, measured by plasmid reconstitution, were found. The parent line had a repair fidelity of 84.7% compared with 58.9% for S40b (P = 0.0003). It is suggested that repair fidelity can be an important determinant of radiosensitivity in human tumour cells.

Carcinoma↗
PubMed1992

The intrinsic alpha/beta ratio for human tumour cells: is it a constant?

The radiation response of 15 mammalian cell lines comprising 11 human tumour, two human fibroblast and two murine lymphoma cell lines, has been analysed using the linear-quadratic equation. As well as using conventional analysis of acute dose-survival curves to derive values for alpha and beta (termed alpha ac and beta ac), low dose-rate and split-dose experiments have been used to derive independent values of alpha and beta (alpha 1dr and beta RR), respectively. alpha 1dr provides a measure of irrecoverable damage, the magnitude of which agreed well with the initial slope of the acute survival curve for most cell lines. beta RR derived from split-dose experiments represents a unique measure of recovery for each cell line. Large differences were found between individual values of beta ac and beta RR, especially in the radiosensitive cell lines. Since beta RR is a functional measure of recovery we suggest that this is the more relevant parameter in studies of dose sparing. The most striking result of this analysis was found in considering the alpha/beta ratios. No relationship was observed between alpha ac and beta ac resulting in values of alpha ac/beta ac ranging from 1 to 175. In contrast a positive correlation was observed between alpha 1dr beta RR in the 11 tumour cell lines, giving an alpha/beta ratio of 9.4 +/- 1.8 Gy. This observation of the relative constancy of the ratio for human tumour cells leads to an hypothesis about the role of initial damage as a determinant of radiosensitivity.

Animals↗
PubMed1989

The repair of identified large DNA adducts induced by 4-nitroquinoline-1-oxide in normal or xeroderma pigmentosum group A human fibroblasts, and the role of DNA polymerases alpha or delta.

4-Nitroquinoline-1-oxide (4NQO) reacts with DNA primarily at the N2 and C8 of guanosine, with a small percent of reaction at the N6 of adenosine. In human cells it has been unclear whether or not all 4NQO-induced adducts are removed by a nucleotide excision repair mechanism. In this paper we demonstrate that the inhibitor of DNA polymerases alpha and delta, aphidicolin, blocks the repair of all 4NQO adducts. Hence excision repair must operate on all of these lesions. After 4NQO the residual excision repair seen in a xeroderma pigmentosum group A cell line virtually totally defective in UV repair was 40-60% of that in normal cells. Therefore there must be some differences between the excision repair operating on UV as opposed to 4NQO-induced DNA damage.

4-Nitroquinoline-1-oxide↗
PubMed1988

Induction and rejoining of DNA double-strand breaks in human cervix carcinoma cell lines of differing radiosensitivity.

Five recently established cell lines of human carcinoma of the cervix of varying radiosensitivity have been used to determine whether the induction or rejoining of DNA double-strand breaks (dsb) shows any correlation with radiosensitivity or radiation recovery capacity. Double-strand DNA breaks have been measured using neutral filter elution at pH 9.6. The number of breaks induced immediately after irradiation with doses of 10 to 40 Gy 60Co gamma rays appeared to show some correlation with radiosensitivity particularly after 10 Gy; the two more radiosensitive lines incurred more breaks than the more radioresistant lines. In addition, the shape of the induction curve with dose was linear for the two sensitive lines but curvilinear for the resistant lines. Despite the dose scales being different, this mirrored their respective cell survival curve shapes. After 30 or 50 Gy irradiation, rejoining of breaks appeared to be rapid and almost complete within 60 min at 37 degrees C for the three resistant lines. However, for the sensitive lines, one line (HX160c) in particular exhibited a reduced rate of dsb rejoining. In addition, a residual level of dsb was present in this line even after allowing rejoining for 3 h. While induction and rejoining of DNA dsb therefore appears to be a factor in determining radiosensitivity, at doses relevant to cellular survival (up to 10 Gy), the greater induction of DNA dsb in radiosensitive lines may play a significant role in determining the cellular response to ionizing radiation.

Cell Line↗
PubMed1987

Bone and gallium scan findings in malignant fibrous histiocytoma. Case report with radiographic and pathologic correlation.

Malignant fibrous histiocytoma (MFH) is the most common soft tissue malignancy in adults. The Ga-67 citrate scan findings of an extremity-located MFH, the most common location of this neoplasm, have never been published in English language journals to the best of the authors' knowledge. Ga-67 citrate and Tc-99m MDP scans of the thigh mass accurately depicted the tumor's local extent, including the presence of central ischemic necrosis within the tumor, and the absence of adjacent osseous involvement and distant metastases, as correlated with computed tomography, angiography, and pathologic examinations.

Femur↗
PubMed1984

Effect of methylprednisolone on swelling after orthognathic surgery.

The effectiveness of methylprednisolone for the reduction of postoperative facial edema was evaluated by the computed tomographic examination of 39 patients who underwent either a Lefort I osteotomy or a transoral vertical osteotomy. Results of the CT scans, which were performed preoperatively and at 24 and 72 hours postoperatively, showed that in the LeFort I osteotomy patients methylprednisolone reduced the degree of facial edema by 61% at 24 hours postoperatively and by 10% at 72 hours. In the transoral vertical osteotomy patients methylprednisolone reduced the degree of facial edema by 38% at 24 hours postoperatively and by 45% at 72 hours. It was concluded that methylprednisolone is effective for the control and management of postoperative facial edema following orthognathic surgery.

Adolescent↗
PubMed1979

Immediate operation for ectopia cordis.

Forty-one infants with thoracoabdominal ectopia cordis have been reported to date; 9 of them survived. Among the patients with an omphalocele as the abdominal wall defect, however, only 2 survived. Death in this group of patients occurred almost exclusively as a consequence of either attempted coverage of the heart or secondary to the associated intracardiac lesion. We report here the case of a patient recently treated in whom coverage with a temporary Silastic prosthesis protected the exposed heart from infection and rupture of the sac, thus permitting full cardiac investigation before operation.

Abdominal Muscles↗