Ignition experiments and models of a plastic bonded explosive (PBX 9502).

Ignition experiments from various sources, including our own laboratory, have been used to develop a simple four-step, pressure-dependent ignition model for PBX 9502, which is composed of 95% by mass triaminotrinitrobenzene (TATB) and a 5% by mass chlorotrifluoroethylene/vinylidine fluoride binder. The four-steps include drying, mono-furazan formation, and decomposition of mono-furazan and TATB into equilibrium products. Our experiments were both sealed and vented and included various ullage percentages ranging from 18% to 75% of unfilled confinement volume. Our sample densities ranged from 38% of the theoretical maximum density (TMD) to 98% TMD. We observed a decrease in ignition times with the higher density samples, an increase in ignition times with increased venting, and an increase in ignition times with increased ullage. From our experiments, we conclude that decomposition of PBX 9502 is pressure dependent, open pore decomposition occurs in low-density experiments, and that closed pore decomposition occurs when the samples are pressed to near full density. In some of our confined high-density experiments we have observed for the first time, multiple temperature excursions prior to ignition caused by internal pressure generation.

Paclitaxel restores radiation-induced apoptosis in a bcl-2-expressing, radiation-resistant lymphoma cell line.

PURPOSE: To restore radiation-induced apoptosis in a bcl-2-expressing, radiation-resistant murine lymphoma cell line (LY-ar) by pretreatment with paclitaxel (Taxol). Because this cell line also has high intracellular levels of glutathione (GSH), reportedly due to the bcl-2 expression and involved in the cell's antioxidant functions, paclitaxel treatment was correlated with GSH levels. METHODS AND MATERIALS: LY-ar cells were pretreated with paclitaxel and then irradiated with 5 Gy. Apoptosis was measured by DNA fragmentation 6 h later. Dose response and time course experiments were performed. Intracellular GSH levels were measured after treatment. Cell survival analysis was performed for various paclitaxel concentrations +/- 5 Gy. RESULTS: LY-ar cells pretreated with 0 nM, 10 nM, 25 nM, and 50 nM paclitaxel for 20 h underwent apoptosis at 2%, 15%, 25%, and 22%, respectively. With the addition of 5-Gy irradiation, LY-ar cell apoptosis increased to 4%, 30%, 49%, and 57%. Maximal apoptosis was detected with a paclitaxel pretreatment time of 20 h. Intracellular GSH levels were reduced by nearly 50% with paclitaxel pretreatment. Surviving fractions (SFs) with 0 nM, 10 nM, 25 nM, and 50 nM paclitaxel and 0 Gy were 1.0, 0.50, 0.08, and 0.05, respectively. SFs with 0 nM, 10 nM, 25 nM, and 50 nM paclitaxel and 5 Gy were 0.009, 0.003, 3 x 10(-5), and 1 x 10(-5), respectively. CONCLUSION: Radiation-induced apoptosis in LY-ar cells was restored by pretreatment with paclitaxel. This correlated with lowered levels of intracellular GSH. Cell survival analysis indicated that the combination of Taxol and radiation on cell killing was greater than additive.

Restoration of bax in prostate cancer suppresses tumor growth and augments therapeutic cell death induction.

BACKGROUND: Cancer cells are characterized by multiple genetic defects which result in altered rates of cell division, cell death and ability to differentiate. These same molecular alterations may also contribute to therapeutic resistance. We examined the potential contribution of the pro-apoptotic gene, bax, to suppressing the growth of prostate cancer cells. MATERIALS AND METHODS: The bax-deficient DU145 prostate cancer cell line was transfected with a hemagluttinin-tagged bax (HA-bax) vector to generate stable expressing bax clones. RESULTS: Ha-bax clones exhibited a significant reduction in tumor growth compared to vector control and parental cells when xenografted into nude mice. HA-bax clones were significantly more sensitive to cell death induction by cis-diamminedichloroplatinum, etoposide, doxorubicin and gamma-radiation than vector control cells. Sensitivity to paclitaxel remained unaltered in the Ha-bax cells. CONCLUSION: These findings suggest that bax may possess a tumor suppressor function in prostatic glandular epithelial cells and be an important determinant of sensitivity to therapeutic cell death induction.

Radiation-induced apoptosis in sensitive and resistant cells isolated from a mouse lymphoma.

Cells were isolated from a mouse lymphoma (LY-TH) and grown in vitro. They were susceptible to radiation-induced apoptosis after low doses with the appearance of endonucleolytically fragmented DNA 1 h after irradiation. Four hours after receiving 5 Gy, 80% of the DNA was endonucleolytically cleaved. Apoptosis induction by DNA double-strand break (dsb) formation was more effective compared with induction by single-strand break (ssb) formation. After long-term culturing, LY-TH cultures became refractory to apoptosis. Apoptosis-permissive cells (LY-as, cloned from LY-TH cells) were three times more radiosensitive than clonally expanded apoptosis-refractory cells (LY-ar). Low dose-rate irradiation and maintenance at 25 degrees C for 5 h postirradiation was sparing in LY-ar but not LY-as cells, suggesting a repair deficiency in LY-as cells. Analysis of dsb rejoining kinetics revealed no difference in the initial phase of dsb rejoining. After 1 h, however, relative dsbs in the LY-as variant increased as endonucleolytic cleavage was initiated. Signalling for radiation-induced apoptosis in LY-as cells was independent of the DNA dsb repair pathway and appeared determined by initial events, whereas in LY-ar cells, because of an inhibition in the apoptotic pathway, survival was enhanced and modifiable by repair processes.

Isolation and characterization of nitrogen mustard-sensitive mutants of Chinese hamster ovary cells.

Three nitrogen mustard-sensitive lines of Chinese hamster ovary cells were isolated from mutagenized cultures using the procedure of Thompson et al. (1980). The lines, designated NM1, NM2 and NM3, were 2.1-, 17- and 6.8-fold more sensitive to nitrogen mustard, respectively, than their parent, wild-type, line as determined by the dose required to kill 90% of the cells, IC90. Patterns of cross-sensitivity to other DNA-damaging agents including ultraviolet light, cis-diamminedichloroplatinum, and other alkylating agents were determined for each line. Analysis of these results suggests that the phenotypes of the mutant lines are different from those lines reported previously.