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Biomedical subjects

H Gunji

Publications and source records attributed to H Gunji.

48 records · Page 3Linked to original sources
PubMed1992

Differentiation and retrodifferentiation of human myeloid leukemia cells is associated with reversible induction of cell cycle-regulatory genes.

Treatment of human myeloid leukemia cells (HL-60, U-937, THP-1) with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with differentiation along the monocytic lineage. This induction by TPA is characterized in part by growth arrest and the appearance of differentiated monocytic phenotype. The present studies demonstrate that myeloid leukemia cells exit the cell cycle to G0-G1 between 24 and 36 h following TPA treatment. This G0-G1 arrest was accompanied by down-regulation of the cell cycle-regulatory genes cdc2, cyclin A, cyclin B, and cdc25. Similar findings were obtained for histones H1 and H4. Cell cycle progression of synchronized U-937 cells revealed low to undetectable mRNA levels for these genes in G1 and maximal transcription in G2-M phase. Results obtained from mRNA half-life studies demonstrate that the stability of cdc2, cyclin A, cyclin B, and cdc25 transcripts is similar in control and TPA-treated U-937 cells. Nuclear run-on assays demonstrated down-regulation of histone gene transcription, while there was no signal detectable for the cell cycle-regulatory genes. The present findings also demonstrate that long term culture of TPA-differentiated U-937 cells is associated with a decrease in G0-G1-arrested cells and an increase of cells in S and G2-M after 25 days. This reentry into the cell cycle was accompanied by loss of adherence, down-regulation of markers for the monocytic phenotype, and induction of the cell cycle-regulatory genes. This process of retrodifferentiation was completed after 36 days when patterns of cell cycle-regulatory and histone gene expression were identical to that in untreated U-937 cells.

Cell Cycle↗
PubMed1992

cis-Diamminedichloroplatinum(II) induces c-jun expression in human myeloid leukemia cells: potential involvement of a protein kinase C-dependent signaling pathway.

cis-Diamminedichloroplatinum(II) (CDDP) is a chemotherapeutic agent known to inhibit DNA, RNA, and protein synthesis. The cytotoxicity of this drug is thought to result from the formation of DNA intrastrand cross-links. The present work demonstrates that treatment of human myeloid leukemia cells (HL-60, U-937, and KG-1) with CDDP is associated with increased expression of the c-jun gene and that this effect is related to activation by a transcriptional mechanism. The results also demonstrate that treatment with CDDP is associated with increases in protein kinase C (PKC) activity. Furthermore, the finding that pretreatment with H7, an inhibitor of PKC, abrogates the effect of CDDP on c-jun expression suggested the involvement of PKC in this process. Down-regulation of PKC by prolonged pretreatment with 12-O-tetradecanoylphorbol-13-acetate was also associated with inhibition of CDDP-induced c-jun expression. The results further demonstrate that there is a temporal relationship between the CDDP-induced increase in c-jun expression and the occurrence of internucleosomal DNA cleavage characteristic of programmed cell death. These findings suggest that c-jun may be involved in the cellular response to DNA-damaging agents, such as CDDP, and that this effect may be mediated by a PKC-dependent pathway.

Actins↗
PubMed1992

A method with three triangular flaps as a secondary operative procedure after reconstruction of the lower lip by Estlander's method.

We have devised a new method for secondary commissuroplasty after reconstruction of the lower lip using Estlander's method with both aesthetically and functionally satisfactory results. This method consists of forming two equilaterally triangular mucosal flaps on the vermilion and a small triangular skin flap in the new position of the commissure and transposing these three flaps to reconstruct the commissure. In the present paper, we reported the procedure and the results. This method produces extremely good results, obtaining favorable commissure form and reconstruction of the mucosa of both upper and lower lips without leaving an unnatural-looking color change in the mucosa or a step deformity in the vermilion. It can be expected that our method will improve the results of Estlander's operations after tumor resection in the lower lip.

Aged↗
PubMed1992

Internucleosomal DNA fragmentation during phorbol ester-induced monocytic differentiation and G0/G1 arrest.

The treatment of human myeloid leukemia cell lines with phorbol esters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), is associated with loss of proliferative capacity and induction of monocytic differentiation. The present results demonstrate that treatment of asynchronous human U-937 leukemia cells with 10 nM TPA is also associated with oligonucleosomal DNA cleavage. This pattern of DNA fragmentation, which is observed in programmed cell death, was detectable in populations of TPA-treated cells that had entered a nonproliferative G0/G1 phase. Similar findings were obtained after TPA treatment of a synchronous population of G1 cells. These cells progressed through S and G2/M phases before undergoing internucleosomal DNA cleavage during G0/G1 arrest. These G0/G1 cells displayed characteristics of monocytic differentiation, including down-regulation of c-myc expression and induction of c-fms transcripts. DNA fragmentation was also studied in cells treated with 5 nM TPA for 48 h and then monitored in drug-free long-term culture. Endonucleolytic cleavage was similarly observed in the differentiated G0/G1 population. However, longer periods of culture were associated with a decrease in DNA fragmentation to undetectable levels. This effect was followed by retrodifferentiation and reentry of cells into cycle. Taken together, these findings demonstrate that internucleosomal DNA fragmentation occurs during induction of monocytic differentiation, and that both of these events are detectable in G0/G1 cells.

Cell Differentiation↗
PubMed1992

Down-regulation of cell cycle control genes by ionizing radiation.

The cellular responses to ionizing radiation include growth arrest, DNA repair, and lethality. However, little is known about the signaling events responsible for these responses. The present studies have examined the effects of ionizing radiation on the expression of genes involved in cell cycle control. The results demonstrate that the treatment of asynchronous cells with 20 Gy ionizing radiation is associated with transient down-regulation of the cdc2, cyclin A, cyclin B, and cdc25 genes. This effect was associated with transient induction of the c-jun gene. RNA stability studies demonstrate that the down-regulation of gene expression following ionizing radiation exposure is at least in part due to a decrease in transcript half-life. Other studies were performed with elutriated cells enriched for populations in G1 and S phases. Treatment of G1 enriched cell populations with 10 Gy resulted in a selective decrease in cyclin B mRNA levels, whereas this effect on cyclin B expression was less pronounced at 5 Gy and undetectable at 1 Gy. Similar results were obtained with S phase enriched cells. Taken together with clonogenic survival studies, these findings indicate that down-regulation of cell cycle control gene expression is associated with lethality, whereas lower doses of ionizing radiation have little, if any, effect on the expression of these genes. The findings also suggest that DNA damage may activate signaling events which regulate expression of cell cycle control genes.

CDC2 Protein Kinase↗
PubMed1991

Camptothecin and its derivatives induce expression of the c-jun protooncogene in human myeloid leukemia cells.

We have recently demonstrated that certain camptothecin derivatives are effective agents in the treatment of human tumor xenografts in nude mice. While camptothecin and its derivatives are recognized as inhibitors of topoisomerase I, little is known about the effects of these agents on specific gene expression, particularly genes involved in growth control. The c-jun early response gene codes for a leucine zipper transcription factor. The present studies demonstrate that 20(S)-camptothecin, 9-amino-20(S)-camptothecin, and 9-nitro-20(S)-camptothecin inhibit the growth of human U-937 myeloid leukemia cells and induce expression of the c-jun gene. c-jun transcripts were increased at 3 h and reached a maximum at 6 h of drug exposure. We also demonstrate that the induction of c-jun gene expression by these agents occurs at the transcriptional level. H7, a nonselective inhibitor of protein kinase C, completely blocked c-jun expression in 20(S)-camptothecin-treated cells, while another protein kinase inhibitor, HA1004, had no detectable effect. Similar findings were obtained for other leucine zipper encoding genes, including jun-B. These results suggest that 20(S)-camptothecin, 9-amino-20(S)-camptothecin, and 9-nitro-20(S)-camptothecin activate a cellular response involving the induction of early response genes. Finally, we demonstrate that induction of c-jun expression occurs in association with internucleosomal DNA fragmentation, a characteristic of programmed cell death.

Camptothecin↗
PubMed1991

Induction of internucleosomal DNA fragmentation in human myeloid leukemia cells by 1-beta-D-arabinofuranosylcytosine.

The present results demonstrate that treatment of human U-937 myeloid leukemia cells with 1-beta-D-arabinofuranosylcytosine (ara-C) is associated with DNA fragmentation at multiples of approximately 200 base pairs. The extent of ara-C-induced DNA fragmentation was dependent on drug concentration and time of exposure. This pattern of internucleosomal DNA cleavage has been observed during programmed cell death and was associated in the present studies with loss of clonogenic survival. The results also demonstrate that the c-jun protooncogene is induced by ara-C during periods of DNA cleavage. These findings suggest that ara-C activates a program involving both oligonucleosomal DNA fragmentation and changes in early response gene expression.

Cell Line↗
PubMed1991

Ionizing radiation induces expression and binding activity of the nuclear factor kappa B.

Recent studies have demonstrated that treatment of mammalian cells with ionizing radiation is associated with activation of gene expression. Although the signal transduction pathways stimulated by ionizing radiation remain unclear, our previous findings indicate that radiation induces specific genes at the transcriptional level. The present work has examined the effects of ionizing radiation on the transcription factor NF-kappa B. The results demonstrate that ionizing radiation activates DNA binding of nuclear factor (NF)kappa B. This effect was detectable at 2 grays (Gy) and reached a maximum at 5-20 Gy. At a dose of 20 Gy, the increase in NF-kappa B binding activity was maximal at 2-4 h and then declined to pretreatment levels. The results also demonstrate that ionizing radiation transiently increases NF-kappa B mRNA levels. However, the finding that induction of NF-kappa B binding to DNA occurs in the presence of cycloheximide indicates that ionizing radiation activates preexisting NF-kappa B protein. NF-kappa B exists as a cytoplasmic protein before activation. Thus, our results suggest that ionizing radiation induces transduction pathways which include cytoplasmic signaling events.

Base Sequence↗
PubMed1991

Protein kinase C activation and protooncogene expression in differentiation/retrodifferentiation of human U-937 leukemia cells.

Human U-937 leukemia cells differentiate along the monocytic lineage following 3-day exposures to 12-O-tetradecanoylphorbol-13-acetate (TPA). This induction of differentiation is accompanied by adherence and loss of proliferation, as well as expression/repression of differentiation-associated genes. Long term culture of TPA-differentiated U-937 cells in the absence of phorbol ester for 32-36 days resulted in a process of retrodifferentiation. The retrodifferentiated cells detached from the substrate and reinitiated proliferation. Other cellular parameters, such as glycosidase activities, cytokine release, and filament expression, returned to levels similar to that observed in uninduced cells. Treatment of U-937 cells with TPA resulted in a rapid translocation of protein kinase C (PKC) from the cytosol to cell membrane fractions within 2-8 min. Increased levels of membrane-associated PKC activity persisted until 17-29 days. However, longer periods of incubation were associated with a return to the distribution of PKC in control cells. Activation of PKC has been implicated in the regulation of certain immediate early response genes, and in the present studies, TPA rapidly induced c-fos and c-jun gene expression. Levels of c-fos and c-jun transcripts remained elevated during periods of PKC activation and also returned to levels observed in control cells by 30-36 days, when the cells entered retrodifferentiation. Staurosporine, a nonspecific inhibitor of PKC, partially blocked TPA-induced adherence and growth inhibition and concomitantly prevented TPA-induced c-fos and c-jun gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1991

Activation of the c-jun protooncogene in human myeloid leukemia cells treated with etoposide.

The epipodophyllotoxin etoposide is an inhibitor of topoisomerase II. The effects of this agent on gene expression, particularly the transcriptional induction of genes implicated in growth control, are unknown. The present results demonstrate that etoposide induces expression of the c-jun protooncogene in HL-60 myeloid leukemia cells. This induction of c-jun expression was maximal at 3 hr and was transient. Similar findings were obtained in the human U-937 myeloid leukemia cell line. Nuclear run-on assays demonstrated that the induction of c-jun expression by etoposide is regulated at the transcriptional level. The results further demonstrate that etoposide-induced c-jun expression occurs in association with the appearance of c-fos transcripts. Moreover, the c-jun gene is induced by etoposide during periods of oligonucleosomal DNA cleavage, which is characteristic of programmed cell death. These findings suggest that transcriptional induction of c-jun expression represents a signaling pathway activated in the cellular response to etoposide-induced DNA damage.

DNA Damage↗