Histochemically detectable changes in the liver of the mouse after subcutaneous injection of a single sublethal does of insulin and the effect of insulin on mitotic rate and chromosome changes in cultured mouse liver cells have been studied. No insulin-induced necrosis or hydropic degeneration of periportal cells was observed. The most marked changes found were a diminution of glycogen and an accumulation of sudanophilic lipid, first in the periportal cells, then throughout the loblue, followed by a rapid restoration to normal. There were no changes in the mitochondria with the sublethal dose. Mitotic rates were increased with 0.5mg% for 10 to 20 hours treatment but no chromosome changes were observed. These observations indicate that insulin causes disturbance of metabolic processes in the liver, which might be interpreted as signs of incipient injury, but insulin does not give any damage at the chromosomal level.
Animal ; Cells, Cultured ; Chromosomes ; Female ; Histocytochemistry ; Insulin/pharmacology* ; Liver/cytology* ; Liver/drug effects ; Male ; Mice ; Mitotic Index/drug effects

OBJECTIVETo investigate the induction effects of sulfur dioxide (SO(2)) inhalation on chromosomal aberrations (CA) in mouse bone marrow cells.

METHODSThe mice were treated with SO(2) for 4 h/day x 7 days at various concentrations of SO(2), then mitotic indices and CA in the bone marrow cells were analyzed.

RESULTSSO(2) increase the frequencies of CA and aberrant cells in mouse bone marrow cells in dose-dependent manner. The frequencies (%) of the aberrant cells in mouse bone marrow cells induced by SO(2) at concentrations of 0, 14, 28, 56 and 84 mg/m(3) were 1.81, 3.00, 3.58, 4.26 and 4.86, respectively. SO(2) at low concentrations induced only chromatid-type CA, but at high concentrations it induced both chromatid-type and chromosome-type CA. SO(2) inhalation decreased the mitotic indices of the bone marrow cells.

CONCLUSIONSSO(2) inhalation may inhibit mitoses and increase CA frequencies of the bone marrow cells; therefore, it is a clastogenetic and genotoxic agent. It implies that long time exposure of SO(2) pollutant at low concentration in air may be a potential risk to induce damage of cytogenetic material in humans.

Administration, Inhalation ; Animals ; Bone Marrow Cells ; drug effects ; metabolism ; pathology ; Chromosome Aberrations ; drug effects ; Dose-Response Relationship, Drug ; Female ; Male ; Mice ; Mitotic Index ; Sulfur Dioxide ; administration & dosage ; pharmacology

The anticancer agent's FT-207, N1-(2'-tetrahydrofuryl)-5-fluorouracil, a derivative of 5FU (5-fluorouracil), induced chromosome damage to the human leukocyte was investigated. FT-207 inhibit mitosis and cause chromatid and chromosome breakage and chromatid exchange with 20 ug/ml for 48 to 72 hours of treatment. However, with 15 ug/ml for 72 hours only delayed spiralization was produced in some of the chromosomes in the same cells. The random distribution of chromosome breakage were observed and the effect of FT-207 on the chromosomes of human leukocytes were time dependent rather than concentration dependent. The comparision of the effect of mitomycin C on human leukocytes and the action of FT-207 at specific times during the cell cycle were discussed.
Cells, Cultured ; Chromosome Aberrations* ; Female ; Fluorouracil/analogs & derivatives* ; Human ; Leukocytes/drug effects ; Leukocytes/ultrastructure* ; Male ; Mitotic Index/drug effects ; Tegafur/pharmacology* ; Time Factors

BACKGROUNDStudies have shown that oxidized low density lipoprotein (ox-LDL) promotes the pathogenesis and development of atherosclerosis (AS), and that the proliferation, migration and phenotype alteration of vascular smooth muscle cells (vSMCs) into foam cells are critical changes in AS. It is proposed that ox-LDL might play a novel role in the pathologic process of vSMCs. The present study was performed ex vivo to investigate the effects of ox-LDL on the growth of cultured human vSMCs.

METHODSUsing NaBr density gradient centrifugation, LDL from human plasma was isolated and purified. ox-LDL was produced from LDL after being incubated with CuSO4. ox-LDL was then added to the culture medium at different concentrations (25 microg/ml, 50 microg/ml, 75 microg/ml, 100 microg/ml, 125 microg/ml, and 150 microg/ml) for 7 days. The influence of ox-LDL on vSMC growth was observed from several aspects as growth curve, mitosis index, lipid staining, and in situ determination of apoptosis. The digital results were analyzed with SPSS 10.0.

RESULTSThe ox-LDL produced ex vivo had a good purity and optimal oxidative degree, which was similar to the intrinsic ox-LDL in atherosclerotic plaque. ox-LDL at a concentration of 25 microg/ml demonstrated the strongest proliferation. At the concentration of 125 microg/ml, ox-LDL suppressed the growth of vSMCs. At concentrations of 25 microg/ml and 50 microg/ml, ox-LDL presented powerful mitotic trigger. When the concentration of ox-LDL increased, the mitotic index of vSMCs decreased gradually. ox-LDL induced more foam cells from vSMCs with rich intracellular lipid accumulation at concentrations of 25 microg/ml and 50 microg/ml. ox-LDL at higher concentrations induced more apoptotic vSMCs.

CONCLUSIONSox-LDL at lower concentrations may trigger proliferation and phenotype alteration into foam cells of vSMCs, and at higher concentrations it may induce apoptosis in vSMCs. ox-LDL plays an important role in the pathogenesis and development of atherosclerosis by its effect on vSMCs proliferation, phenotype alteration and apoptosis.

Apoptosis ; drug effects ; Atherosclerosis ; etiology ; Cell Proliferation ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Humans ; Lipoproteins, LDL ; toxicity ; Mitotic Index ; Muscle, Smooth, Vascular ; cytology ; drug effects ; Myocytes, Smooth Muscle ; cytology ; drug effects

AIMTo evaluate the genetic instability of 11 fertile and 25 infertile men.

METHODSThe methodology of sister chromatid exchanges (SCEs) was applied to cultures of peripheral blood lymphocytes, and the levels of SCEss were analyzed as a quantitative index of genotoxicity, along with the values of the mitotic index (MI) and the proliferation rate index (PRI) as qualitative indices of cytotoxicity and cytostaticity, respectively. The genotoxic and antineoplastic agent, mitomycin C (MMC), and caffeine (CAF)--both well-known inhibitors of DNA repair mechanism--were used in an attempt to induce chromosomal instability in infertile men, so as to more easily detect the probable underlying damage on DNA.

RESULTSOur experiments illustrated that infertile men, compared with fertile ones, demonstrated a statistically significant DNA instability in peripheral blood lymphocytes after being exposed simultaneously to MMC and CAF.

CONCLUSIONThe current study showed vividly that there was genetic instability in infertile men which probably contributes to the development of an impaired reproductive capacity.

Adult ; Caffeine ; pharmacology ; Chromosome Aberrations ; drug effects ; DNA Repair ; drug effects ; Humans ; Infertility, Male ; genetics ; Lymphocytes ; cytology ; drug effects ; Male ; Middle Aged ; Mitomycin ; pharmacology ; Mitotic Index ; Sister Chromatid Exchange ; drug effects

AIMTo investigate the radiosensitizing effect and mechanism of action of staurosporine (STP) in human colon carcinoma HT-29 and breast cancer MCF-7/ADR cells.

METHODSThe effect of STP on the cytotoxicity of X-ray was determined by clonogenic assay. The effect of STP on cell cycle arrest induced by X irradiation was studied in two cell lines by using flow cytometry, Western Blotting was performed to indicate the changes of cyclin B1 and cdc2 protein levels.

RESULTSSTP sensitized the two cell lines to X-ray by clonogenic assay. STP potentiated the cytotoxicity of X-ray by 2.10- and 2.09-fold in HT-29 and MCF-7/ADR cells. Flow cytometry assay showed that exposure of HT-29 and MCF-7/ADR cells to X-ray caused cells arrest in G2 phase. The percentage of arrest G2 phase cells were 56% and 52.7%, respectively. The addition of STP after irradiation resulted in a dose-dependent reduction of G2 phase arrest induced by X-ray. Furthermore, the results showed that STP blocked decrease of cyclin B1 expression induced by X-ray, while mitotic index measurement indicated that X-ray-irradiated cells treated with STP entered mitosis. The data suggested that the potentiation of cytotoxicity of X-ray by STP is associated with the suppression of cyclin B1 expression, which result in the abrogation of G2 arrest, before the cells entered into M phase, they had not enough time to repair.

CONCLUSIONSTP is a potent G2 checkpoint abrogator and markedly enhanced the cytotoxicity of X irradiation in the p53 mutant cancer cells.

Breast Neoplasms ; pathology ; Cyclin B ; biosynthesis ; Cyclin B1 ; Enzyme Inhibitors ; pharmacology ; Female ; G2 Phase ; drug effects ; HT29 Cells ; Humans ; Mitotic Index ; Particle Accelerators ; Radiation Tolerance ; drug effects ; Radiation-Sensitizing Agents ; pharmacology ; Staurosporine ; pharmacology ; Tumor Cells, Cultured

Liver cancer is one of the most common neoplastic diseases with high mortality in China. Currently, antimicrotubule drugs such as paclitaxel (PTX) and vincristine (VCR), are used as the common agents in the clinical chemotherapy for liver cancer. However, the responses of patients to these drugs vary markedly. Successful identification of intracellular factors influencing liver cancer's sensitivity to antimicrotubule drugs would be of great clinical importance. In this study, by engineering human hepatoma cell HepG2 to overexpress synuclein-gamma (SNCG), we investigated if SNCG is a molecular factor associated with the sensitivity to antimicrotubule drug treatment. Real-time RT-PCR and Western blotting assays showed SNCG was successfully overexpressed in HepG2/ SNCG cells compared with HepG2/Neo cells. The overexpressed SNCG altered the proliferation activity in HepG2 cells, which was 66% higher than that of HepG2/Neo cells through MTT method. The overexpressed SNCG also reduced sensitivity of HepG2 cells to antimicrotubule drugs: after PTX or VCR treatment, the proportion of HepG2/SNCG cells in G2/M arrest was significantly lower than that in HepG2/Neo cells. Correspondingly, HepG2/SNCG cells showed significantly lower mitotic index than HepG2/Neo cells. Meanwhile, HepG2/SNCG cells showed higher resistance to PTX and VCR than HepG2/Neo cells, with resistance index 21 and 15 respectively. Our studies suggested that the overexpression of SNCG could confer resistance to antimicrotubule drugs in hepatoma cells; and it indicated that SNCG may be as a potential response marker for antimicrotubule drugs in liver cancer chemotherapy.
Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Cycle ; Cell Proliferation ; Drug Resistance, Neoplasm ; Gene Expression Regulation, Neoplastic ; Genetic Vectors ; Hep G2 Cells ; drug effects ; metabolism ; Humans ; Microtubules ; drug effects ; Mitosis ; drug effects ; Mitotic Index ; Paclitaxel ; pharmacology ; Plasmids ; RNA, Messenger ; metabolism ; Transfection ; Vincristine ; pharmacology ; gamma-Synuclein ; biosynthesis ; genetics ; physiology