Heterogeneity of glutathione S-transferase enzyme and gene expression in ovarian carcinoma.

Expression of the three major cytosolic classes of glutathione S-transferases (GST; Pi, Alpha and Mu) was examined by 2D gel analysis and Western blotting of biopsies from 26 patients diagnosed with ovarian carcinoma. In contrast to other tissues, at least one 'constitutive' subunit from each of the three major cytosolic GST classes was expressed. In most cases, pi appeared to be the major form present, although levels of alpha and mu subunit expression were approximately equal to pi in some patients.

Effects of chlorinated hydrocarbons on cellular volume regulation in slices of rat liver.

The effects of carbon tetrachloride and 1,2-dichloroethane (1,2DCE) on the recovery of slices of rat liver from cellular swelling in vitro were studied. Slices took up water during pre-incubation at 1 degrees C, then cellular volume and ultrastructure were rapidly restored during subsequent incubation at 38 degrees C. Ouabain (2 mm) inhibited water extrusion by less than 50%, while inducing formation of peri-canalicular vesicles, apparently derived from the Golgi apparatus.

Characterization of glutathione S-transferase expression in lymphocytes from chronic lymphocytic leukemia patients.

Chronic lymphocytic leukemia (CLL) is a disease state which frequently responds to alkylating agent chemotherapy but ultimately becomes refractory through acquired resistance mechanisms. In the present study, we have examined the expression of glutathione S-transferases (GST) in both CLL and normal control lymphocytes, as these enzymes have been implicated in mechanisms of natural and acquired resistance. Lymphocyte GST was purified from samples by high-pressure liquid affinity chromatography, and subunits were identified by two-dimensional gel electrophoresis and immunoblotting by using polyclonal antibodies specific for individual subunits.

Involvement of the cellular vacuolar system with the cytotoxicity of bleomycin-like agents.

The role of acidic cellular organelles in regulating the toxicity of selected antitumor drugs was studied with L1210 cells using modifiers of vesicular pH or function. A 1 hr exposure to a non-toxic concentration of the acidotropic weak base ammonium chloride increased the lethality of bleomycin A2 (BLM A2), demethyl BLM A2, peplomycin, and talisomycin S10b to L1210 cells grown in culture. Enhanced BLM lethality was also seen with the lysosomal disruptive agents verapamil and diltiazem.

Initial single-strand DNA damage and cellular pharmacokinetics of bleomycin A2.

The cellular association and fate of high specific activity [3H]bleomycin A2 (BLM A2) were examined in three previously untreated cultured cell lines. Human head and neck A-253 carcinoma cells were 10-fold more sensitive to a 1-hr exposure to BLM A2 than either murine leukemic L1210 or human ovarian SK-OV cells. Both murine and human cells displayed rapid drug association with steady-state drug levels being reached within 15-30 min.