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James B Mitchell

Publications and source records attributed to James B Mitchell.

75 records · Page 5Linked to original sources

Low-energy X-radiation for prevention of restenosis results in localized inhibition of V79 fibroblast cell proliferation.

Local delivery of high-energy ionizing radiation by using 3 or 3 emitters to injured vessels demonstrated inhibition of cell proliferation (CP) and neointima formation. Low-energy ('soft') X-radiation (LEXR) offers logistic and safety advantages over the use of disposable radioisotopes. This study evaluated the efficacy of LEXR in penetration and inhibition of CP at doses similar to those prescribed for the use of radioisotopes for prevention of restenosis. Serial measurements in an ion chamber detected the attenuation of LEXR using potentials of 17 and 40 kV at a distance of 17 cm of air through 0-10 mm depths of serum-containing tissue culture medium. The effect of inhibition on CP was determined by exposing V79 fibroblasts to a potential of 17 kV in order to deliver a prescribed dose of 13 Gy at a dose rate of 2.17 Gy/min to the surface of the cells. Complete inhibition of CP at a height of 0.00 mm occurred with 13 Gy; however, a 50% attenuation of the dose was measured at a medium depth of 1.22 mm and was associated with a reduction of 60% of the CP. LEXR demonstrated an ability to inhibit CP at doses equivalent to those used in techniques involving 3 and 3 irradiation. Under such conditions, the dose gradient is too high, especially for large vessels. However, a catheter-based LEXR that could be inserted into the artery with the capability of varying effective energy would be ideal for intravascular applications.

Journal Article↗

Radiation-induced changes in gene-expression profiles for the SCC VII tumor cells grown in vitro and in vivo.

SCCVII tumor cells that grow in vitro or in vivo as a solid tumor were used to compare and contrast geneexpression profiles with or without exposure to two doses of ionizing radiation. Exponentially growing SCCVII cell cultures and tumors (1 cm diameter) were treated with 0, 2, or 10 Gy, and RNA was collected 1, 3, 6, 12, and 24 h after treatment. Growth under in vitro conditions increased the expression of genes associated with the unfolded protein response (UPR) including ATF4, Ero-1 like, and cystathionase. Growth in vivo indicated that the HIF-1a genes were not upregulated, whereas genes such as hemoglobin alpha and crystallin alpha B were significantly upregulated. Ninety genes of 16K were found to be significantly modulated under either growth condition by radiation treatment. Gene expression was not dose dependent. Sixty percent of these genes exhibited similar modulation under both in vitro and in vivo conditions; however, 29% of the genes were modulated by radiation under in vivo conditions only. Gene-expression profiles for the same tumor cells can differ, dependent on growth conditions, underscoring the influence that the tumor microenvironment exerts on gene expression for both growth of solid tumors and their response to radiation treatment.

Animals↗

Nitroxides as antioxidants: Tempol protects against EO9 cytotoxicity.

Nitroxide free radicals have been shown to be potent antioxidants in a variety of experimental models using diverse means of insults. Among other insults, nitroxides have been shown effective in inhibiting cytotoxicity of quinone-based drugs such as streptonigrin and mitomycin C. These drugs and other chemotherapeutic agents have the potential to undergo bioreductive activation by the normal reducing enzymes within a cell. In the present work we studied the effect of the nitroxide Tempol on the cytotoxicity induced by EO9, a mitomycin C analogue, in HT29 cells under aerobic and hypoxic conditions. The study was aimed to better understand the mechanism of EO9 cytotoxicity and the molecular level of the nitroxide's mode of protection. The reactions of Tempol with activated EO9, and the reactive species formed during EO9 activation were studied in a cell-free solution, using spin-trapping, and electron paramagnetic resonance (EPR) spectrometry. Our results indicate that EO9 induced similar cytotoxicity in HT29 cells under aerobic and hypoxic conditions while Tempol provided similar and almost complete protection to both aerobic and hypoxic cells. The results indicate that EO9 cytotoxicity is due to both 1- and 2-electron reductive activation processes, with aerobic toxicity caused by back-oxidation of the hydroquinone to the semiquinone, EO9.-. Tempol serves both as a useful tool in the study of the mechanisms of quinone-mediated cytotoxicity and as a potent antioxidant against the damaging effects of redox cycling quinones and semiquinones by scavenging of EO9.- or detoxification of O2.- and H2O2.

Aziridines↗