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S W Edmondson

Publications and source records attributed to S W Edmondson.

7 recordsLinked to original sources
PubMed1991

Alterations in keratin expression in hamster tracheal epithelial cells exposed to benzo[a]pyrene.

Changes in keratin expression were documented in cultures of hamster tracheal epithelial (HTE) cells exposed to vitamin A (retinol 10(-6) M) and benzo[a]pyrene (B[a]P), two agents known to affect the differentiation of tracheal epithelial cells in vivo. Keratin protein patterns were determined after 10 days in culture in the presence and absence of B[a]P in order to determine whether the expression of these proteins was altered by this carcinogen. HTE cells maintained in the presence of vitamin A expressed four simple epithelial keratins (7,8,18 and 19) while vitamin A deficient HTE cells expressed four additional cytokeratins (5,6,14 and 17). No effect of B[a]P on keratin expression was observed in vitamin A treated cells. However, vitamin A deficient HTE cells exposed to B[a]P (0.05-10 micrograms/ml) demonstrated a decrease in the expression of the four differentiation-related keratins while the simple epithelial keratins appeared to be unaffected. These observations were verified at the RNA level employing Northern blot analysis using cDNA probes for human keratins 5,6 and 14. Results demonstrate that B[a]P alters the expression of differentiation-related genes, the cytokeratins, in cell types known to develop into tumors of the respiratory tract.

Animals↗
PubMed1990

Regulation of differentiation and keratin protein expression by vitamin A in primary cultures of hamster tracheal epithelial cells.

Hamster tracheal epithelial (HTE) cells maintained in primary culture show the induction of specific keratin species under vitamin A-deficient conditions. A comparison was made between the morphology and the expression of keratins in HTE cells in vivo and in primary culture with and without vitamin A. HTE cells cultured in serum-free, vitamin A-supplemented medium formed a simple cuboidal, ciliated monolayer and produced four simple epithelial keratins (7, 8, 18, and 19). In contrast, vitamin A-deficient HTE cells, which were squamous-like and stratified in culture, produced a more complex keratin pattern, with the induction of four additional keratin species (5, 6, 14, and 17). A keratin pair whose expression serves as a marker of stratified epithelia was induced, as well as a single keratin species unique to lesions of squamous metaplasia in vitamin A-deficient hamster tracheal organ cultures. Thus it appears that HTe cells retain the ability to respond to a deficiency in vitamin A through squamous differentiation and increased keratin production when removed from the intact organ and maintained in primary culture in a chemically defined medium. This system may be useful for the study of mechanisms underlying the squamous differentiation of respiratory epithelial cells in the development of bronchogenic tumors.

Animals↗
PubMed1987

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Acquired Immunodeficiency Syndrome↗
PubMed1986

Radioprotection in rat spinal cord with WR-2721 following cerebral lateral intraventricular injection.

The capacity of WR-2721 to provide radioprotection in central nervous system (CNS) tissue was assessed in F-344 rats irradiated with Cs-137 to the cervical spinal cord 45 min following injection of either 0.33 mg (0.60 X LD50) of WR-2721 or carrier solution in the right lateral cerebral ventricle. The radiation dose groups were 20, 26, 32, or 38 Gy; the dose rate was 1.48 Gy/min. Following irradiation, the time in weeks to forelimb and hindlimb paralysis was measured and statistical significance was assessed by means of the log rank sum test. The median times in weeks to forelimb paralysis in control vs. WR-2721-treated rats were, respectively, 20 vs. 22 at 38 Gy, 19 vs. 31 at 32 Gy (p less than 0.01), 23 vs. 28 at 26 Gy (p less than 0.01), and 49 vs. 60 at 20 Gy (p less than 0.01). The median times to hindlimb paralysis in control vs. WR-2721-treated rats were respectively, 20 vs. 29 at 38 Gy (p less than 0.001), 20 vs. 35 at 32 Gy (p less than 0.01), 23 vs. 34 at 26 Gy (p less than 0.001), and 58 vs. 65 at 20 Gy (p less than 0.01). From these results, we calculated the DMF for forelimb paralysis to be 1.3 and for hindlimb paralysis, 1.6. Histological studies from selected spinal cords from symptomatic killed rats showed petechial hemorrhages, rare microvascular thrombi, and scattered microinfarcts in both gray and white matter. In the white matter columns, there were scattered microfoci of demyelination. The histological findings did not differ between the control and WR-2721-treated groups, but were worse in the higher dose groups. These data indicate that WR-2721 has the capacity to be radioprotective in CNS tissues, when it is administered by a route that bypasses the blood-brain barrier.

Amifostine↗
PubMed1986

Toxicity and biodistribution of the radioprotectors, WR2721, WR77913, and WR3689, in the CNS following intraventricular or intracisternal administration.

The radioprotective capacity of the phosphorothioate compounds, WR2721, WR77913, and WR3689, in the CNS is being evaluated following injection of the drugs into the lateral cerebral ventricle or the cisterna magna of F-344 rats. This approach circumvents the blood-brain barrier and permits an assessment of the CNS toxicity and regional distribution of these compounds. Following intraventricular injection in 150-200 gm female rats, the LD50 doses for WR2721, WR77913, and WR3689 were respectively 0.60 +/- 0.07 mg (S.E.), 2.36 +/- 0.13 mg, and 3.56 +/- 0.26 mg. Following intracisternal injection the LD50 doses were 0.71 +/- 0.18 mg, 4.12 +/- 1.09 mg and 3.03 +/- 0.68 mg, respectively. WR 2721 produced lethargy, unsteady gait, and dishevelment but these signs all resolved completely within 1-3 days in survivors. In addition to these signs, WR77913 and WR3689 produced severe convulsions. At high doses, following intraventricular administration, all three drugs were associated with cerebral and diencephalic periventricular necrosis and ipsilateral necrosis of the lateral hippocampus. Biodistribution studies were performed with [S-35]-labeled derivatives of the drugs and tissue sampling. The three drugs demonstrated similar patterns. Forty-five minutes following either the intraventricular or intracisternal route of drug delivery the highest drug concentrations were in the brainstem, cerebellum, and cervical cord. Additional studies with autoradiography revealed that intraventricular injection was associated with high drug uptake in the cerebral white matter, the periventricular diencephalon, and the periaqueductal mesencephalon. The biodistribution and toxicity data together suggest that the drugs can be ranked, WR3689 greater than WR77913 greater than WR2721, according to the level of drug thiol that can be achieved in the CNS tissues with intraventricular or intracisternal injection. Tissue levels achievable with WR2721 following these two routes of administration are as high as levels others have reported as radioprotective in rodent skin and gut.

Amifostine↗