phosphorus-radioisotopes and Necrosis

To study the effects of phosphorus-32 glass microspheres ((32)P-GMS) on human hepatocellular carcinoma in nude mice.. Human liver cancer cell line was implanted into the dorsal subcutaneous tissue of 40 BALB/c nude mice. Then the 40 tumor-bearing BALB/ c nude mice were allocated into treatment group (n=32) and control group (n=8). In the former group different doses of (32)P-GMS were injected into the tumor mass, while in the latter nonradioactive (31)P-GMS was injected into the tumor mass. The experimental animals were sacrificed on the 14th day. The ultrastructural changes of tumor in both treatment group and control group were studied with transmission electron microscopy (TEM) and stereology.. In treatment group, a lot of tumor cells were killed and the death rate of tumor cells was much higher (35-70%). Ultrastructurally, severe nuclear damage was observed in the death cells. The characteristics of apoptosis such as margination of heterochromatin was also found in some tumor cells. Besides, well differentiated tumor cells, degenerative tumor cells and some lymphocytes were seen. The skin and muscle adjacent to the tumor were normal. In control group, the tumor consisted of poorly differentiated tumor cells, in which there were only a few of dead cells(5%). Stereological analysis of ultrastructural morphology showed that Vv of nuclei (53.31+/-3.46) and Vv of nucleoli(20.40+/-1.84) in the control group were larger than those(30.21+/-3.52 and 10.96+/-2.52) in the treatment group respectively (P<0.01), and Vv of RER (3.21+/-0.54) and Vv of mitochondria (4.53+/-0.89) in the control group were smaller than those (8.67+/-1.25 and 7.12+/-0.95) in the treatment group respectively (P<0.01, 0.05). Sv of the membrane of microvilli and canaliculi (27.12 um(2)/100 um(3)+/-11.84 um(2)/100 um(3)) in the control group was smaller than that (78.81 um(2)/100 um(3)+/- 19.69 um(2)/100 um(3)) in the treatment group (P<0.01). But Vv of lipid particles (3.71+/-1.97) and Vv of vacuoles (5.72+/-1.58) were much larger than those (0.30+/-0.16 and 0.35+/-0.15) in the treatment group respectively (P<0.05, P<0.01).. The experimental results indicate that local administration of (32)P-GMS can produce obvious effect on liver cancer cells and the anticancer effect of (32)P-GMS is directly proportional to the dose administrated. Ultrastructural stereology can also show the effect of (32)P-GMS on the normalization of tumor cells, which is beneficial to the prognosis and treatment of patients. Moreover, local administration of (32)P-GMS is also safe.

Topics: Animals; Carcinoma, Hepatocellular; Cell Line, Tumor; Humans; Liver Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Electron; Microspheres; Microvilli; Mitochondria; Necrosis; Neoplasm Transplantation; Phosphorus Radioisotopes

Biochemical markers improve the classification and staging of breast cancer and may refine management decisions if it can be shown that they correlate with accepted prognostic factors or patient outcome. Using phosphorus-31 magnetic resonance spectroscopy ((31)P MRS), we determined the phospholipid content of 43 malignant breast tumors, correlating the profiles with specific histopathologic and clinical features and hormone receptor status. Among the 14 phospholipids identified, the mean mole percentage of sphingomyelin, phosphatidylcholine, phosphatidylserine, phosphatidic acid, phosphatidylglycerol, and alkylacylphosphatidylcholine predicted cellular infiltration, infiltration type, elastosis, lymphatic invasion, perineural invasion, necrosis, and estrogen receptor positivity. (31)P MRS phospholipid profile data provide statistical correlations among histologic features and molecules known to play important roles in cellular communication, regulation, and processes unique to malignant tissues.

Topics: Breast Neoplasms; Granulocytes; Humans; Lymphatic Metastasis; Magnetic Resonance Imaging; Multivariate Analysis; Necrosis; Phosphatidic Acids; Phosphatidylcholines; Phosphatidylglycerols; Phosphatidylserines; Phospholipids; Phosphorus Radioisotopes; Receptors, Estrogen; Sphingomyelins

We examined effects of two insulin-like growth factors, insulin and insulin-like growth factor-I (IGF-I), against apoptosis, excitotoxicity, and free radical neurotoxicity in cortical cell cultures. Like IGF-I, insulin attenuated serum deprivation-induced neuronal apoptosis in a dose-dependent manner at 10-100 ng/mL. The anti-apoptosis effect of insulin against serum deprivation disappeared by addition of a broad protein kinase inhibitor, staurosporine, but not by calphostin C, a selective protein kinase C inhibitor. Addition of PD98059, a mitogen-activated protein kinase kinase (MAPKK) inhibitor, blocked insulin-induced activation of extracellular signal-regulated protein kinases (ERK1/2) without altering the neuroprotective effect of insulin. Cortical neurons underwent activation of phosphatidylinositol (PI) 3-kinase as early as 1 min after exposure to insulin. Inclusion of wortmannin or LY294002, selective inhibitors of PI 3-K, reversed the insulin effect against apoptosis. In contrast to the anti-apoptosis effect, neither insulin nor IGF-I protected excitotoxic neuronal necrosis following continuous exposure to 15 microM N-methyl-D-aspartate or 40 microM kainate for 24 h. Surprisingly, concurrent inclusion of 50 ng/mL insulin or IGF-I aggravated free radical-induced neuronal necrosis over 24 h following continuous exposure to 10 microM Fe2+ or 100 microM buthionine sulfoximine. Wortmannin or LY294002 also reversed this potentiation effect of insulin. These results suggest that insulin-like growth factors act as anti-apoptosis factor and pro-oxidant depending upon the activation of PI 3-kinase.

Topics: Adenosine Triphosphate; Androstadienes; Animals; Apoptosis; Buthionine Sulfoximine; Calcium-Calmodulin-Dependent Protein Kinases; Cells, Cultured; Chromones; Enzyme Activation; Enzyme Inhibitors; Excitatory Amino Acid Agonists; Flavonoids; Hypoglycemic Agents; Insulin; Insulin Antagonists; Insulin-Like Growth Factor I; Iron; Mice; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Morpholines; N-Methylaspartate; Necrosis; Neocortex; Neurons; Neuroprotective Agents; Oxidative Stress; Phosphatidylinositol 3-Kinases; Phosphorus Radioisotopes; Phosphorylation; Staurosporine; Wortmannin

We used 32P-postlabelling to compare DNA binding between the potent hepatocarcinogen 2,6-dinitrotoluene and its noncarcinogenic analog 2,6-diaminotoluene. The two compounds were compared to determine whether differences in DNA binding could partly explain the differences in their carcinogenicity. Fischer-344 rats were administered 1.2 mmol/kg of a compound by single i.p. injection and examined for DNA adduct formation in the liver. Four adducts were detected following administration of 2,6-dinitrotoluene, with a total adduct yield of 13.5 adducted nucleotides per 10(7) nucleotides. Qualitatively identical adducts were also detected after treatment with the derivative 2-amino-6-nitrotoluene. Adduct yields from 2,6-dinitrotoluene were 30 times greater than from 2-amino-6-nitrotoluene. No adducts were observed following treatment with 2,6-diaminotoluene. 2,6-Dinitrotoluene and 2,6-diaminotoluene were also compared for qualitative differences in hepatotoxicity. 2,6-Dinitrotoluene produced extensive hemorrhagic necrosis in the liver, whereas no evidence of hepatocellular necrosis was detected following administration of the latter. The differences between the two compounds in both DNA binding and cytotoxicity were consistent with the differences in their carcinogenicity.

Topics: Animals; Carcinogens; Chromatography, Ion Exchange; Dinitrobenzenes; DNA; Liver; Male; Necrosis; Phenylenediamines; Phosphorus Radioisotopes; Rats; Rats, Inbred F344

We previously reported that phenylmethylsulfonyl fluoride (PMSF) administration to rats (100 mg/kg, ip in olive oil) as late as 6 or 10 hr after CCl4 (1 ml/kg, ip as a 20% v/v solution in olive oil) can partially prevent the necrogenic response to the hepatotoxin at 24 hr. Here we confirm that observation by electron microscopy and provide further evidence that only in these circumstances were nuclear clumping of chromatin, slight dilatation of the endoplasmic reticulum, myelin figures and lipid droplets in the cytoplasm, large numbers of lysosomes and peroxisomes, glycogen, and slightly swollen mitochondria observable in the protected animals. A very minor part of the late protective effects of PMSF might be due to the effects of this drug on decreasing the intensity of covalent binding of CCl4-reactive metabolites or the intensity of CCl4-induced lipid peroxidation still occurring 6 or 10 hr after CCl4. PMSF administration did not prevent CCl4-induced decreases in cytochrome P450 content or glucose-6-phosphatase activity but partially prevented CCl4-induced calcium accumulation in liver. PMSF treatment increased glutathione and glycogen content in CCl4-poisoned animals, but did not markedly modify protein/phospholipid synthesis or degradation processes. Results suggest that the late protective effects of PMSF administration in CCl4-induced liver necrosis might be due to a favorable modulation of the calcium-calmodulin system similar to that previously described for other drugs.

Topics: Administration, Oral; Animals; Body Temperature; Calcium; Carbon Radioisotopes; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Cytochrome P-450 Enzyme System; Glucose-6-Phosphatase; Glutathione; Leucine; Lipid Peroxidation; Lipids; Liver; Male; Microscopy, Electron; Microsomes, Liver; Necrosis; Phenylmethylsulfonyl Fluoride; Phosphorus Radioisotopes; Rats; Rats, Inbred Strains; Sulfones; Time Factors

Arterial vascular occlusion of hypernephromas may be performed by obstructiing the tumor vascular tree with the injection of ferromagnetic silicone microspheres. The powerful superconducting electromagnet confines the embolized iron-silicone compound to the neoplastic target organ. Radioactive material may or may not be added to the iron-silicone compound to give local direct radioactive radiation therapy to the tumor area. In experimental dogs up to 70,000 rad of beta radiation from the P32 source had been delivered homogeneously within the kidney when mixed with the ferrosilicone. This technique may well be used in cases in which a major operation is contraindicated or when preoperative necrosis of the tumor is advisable. Since the entire procedure can be done with the patient under local anesthesia in a radiology department it may be a valuable new technique in the future management of urological tumors, unilateral renal hypertension, solitary kidney pathology and so forth. Ferrosilicone material has not been found to be toxic. The application of a powerful superconducting electromagnet to the technique provides a means of confining the embolized iron-silicone compound to the target organ.

Topics: Adenocarcinoma; Animals; Catheterization; Dogs; Embolism; Evaluation Studies as Topic; Femoral Artery; Humans; Injections, Intra-Arterial; Iron; Kidney; Kidney Neoplasms; Magnetics; Microspheres; Necrosis; Phosphorus Radioisotopes; Renal Artery; Silicones

Topics: Bone and Bones; Bone Diseases; Calcium Radioisotopes; Diagnosis, Differential; Humans; Infections; Necrosis; Phosphorus Radioisotopes; Prostheses and Implants; Radioisotopes; Radionuclide Imaging; Strontium Isotopes; Strontium Radioisotopes

Topics: Adipose Tissue; Adult; Agammaglobulinemia; Arteritis; Arthritis, Rheumatoid; Autopsy; Blood Platelet Disorders; Bronchopneumonia; Chlorambucil; Chronic Disease; Colon; Dexamethasone; Female; Hematopoiesis; Humans; Lung; Lung Diseases, Obstructive; Lymph Nodes; Lymphoma, Non-Hodgkin; Necrosis; Panniculitis, Nodular Nonsuppurative; Phosphorus Radioisotopes