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PubMed2005

Gene expression in normal human bronchial epithelial (NHBE) cells following in vitro exposure to cigarette smoke condensate.

Cigarettes that burn tobacco produce a complex mixture of chemicals, including mutagens and carcinogens. Cigarettes that primarily heat tobacco produce smoke with marked reductions in the amount of mutagens and carcinogens and demonstrate reduced mutagenicity and carcinogenicity in a battery of toxicological assays. Chemically induced oxidative stress, DNA damage, and inflammation may alter cell cycle regulation and are important biological events in the carcinogenic process. The objective of this study was to characterize and compare the effects of smoke condensates from cigarettes that burn tobacco and those that primarily heat tobacco on gene expression in NHBE cells. For this comparison, we used quantitative RT/PCR and further evaluated the effects on cell cycling using flow cytometry. Cigarette smoke condensates (CSCs) were prepared from Kentucky 1R4F cigarettes (a tobacco-burning product designed to represent the average full-flavor, low "tar" cigarette in the US market) and Eclipse (a cigarette that primarily heats tobacco) using FTC machine smoking conditions. The CSC from 1R4F cigarettes induced statistically significant increases in the mRNA levels of genes responsive to DNA damage (GADD45) and involved in cell cycle regulation (p21;WAF1/CIP1), compared to the CSC from Eclipse cigarettes. In addition, genes coding for cyclooxygenase-2 (COX-2) and interleukin 8 (IL-8), which are associated with oxidative stress and inflammation, respectively, were increased statistically significantly more by CSC from 1R4F than by that from Eclipse. Furthermore, a dose-dependent increase in IL-8 protein secretion into cell culture media was stimulated by 1R4F exposure, whereas minimal IL-8 protein was secreted after Eclipse treatment. The biological relevance of the differential effect on gene expression was reflected in differential cell cycle regulation, as cells exposed to 1R4F CSC exhibited more significant S phase and G2 phase accumulation than cells exposed to Eclipse CSC. These data indicate that the simplified smoke chemistry of the tobacco-heating Eclipse cigarette yields statistically significant reductions in the expression of key genes involved in DNA damage, oxidative stress, inflammatory response, and cell cycle regulation in normal human bronchial epithelial cells compared to a representative tobacco-burning cigarette.

Base Sequence↗
PubMed1975

Movement of beta-irradiated epidermal basal cells to the spinous-granular layers in the absence of cell division.

Guinea-pig epidermis was irradiated with 3000 rad of beta rays 1 hr after two injections of [3-H]thymidine 5 hr apart (labeled cells in S phase and G2 phase) or 18 hr after injection (labeled early G1 cells). In nonirradiated epidermis labeled basal cells divided within 24 hr with daughter cells remaining in the basal layer, and approximately 50% of the labeled cells moved into the spinal layer by the 3rd day. Cell division in nonirradiated epidermis diluted the number of silver grains/nucleus, and lightly labeled cells were found in the granular layer by day 7. Beta irradiation inhibited cell division but it did not slow the rate of transit (ca 8 days) of irradiated labeled cells from basal to granular layer, some of these remaining heavily labeled. Although cell division may play some role in upward movement of basal cells in normal epidermis detachment of a basal cell from the basement membrane and its transit to the granular layer is unimpaired in the absence of cell division. These findings suggest that some radioresistant metabolic function(s), not cell division, is responsible for upward movement of basal cells.

Animals↗
PubMed1981

Cell cycle analysis of cultured mammalian cells after exposure to 4,5',8-trimethylpsoralen and long-wave ultraviolet light.

Cell cycle analysis was used to study the the effect of 4,5'8-trimethylpsoralen (TMP) and long-wave ultraviolet light (UV-A) on cultured mammalian cells. DNA distribution patterns were measured for murine melanoma cells (a cloned line of Cloudman S91) and a strain of diploid human skin fibroblasts (CRL 1295) using both a microfluorimetry procedure and flow cytometry. The untreated cells and those receiving TMP along and UV-A alone had identical DNA content as assessed at several posttreatment intervals (0-72 hr). The majority of cells in control groups contained a G1 DNA content, whereas exposure to TMP (2 x 10(-7) M) plus UV-A (1 Joule/cm2) led to the accumulation of cells in the G2 phase. These observations were similar for each cell type and both analytical techniques were in excellent agreement. The finding that psoralen plus UV-A induces a phase-specific G2 blockade in cultured cells has important implications for understanding the mechanisms which account for enhanced pigmentation and suppression of cellular proliferation following exposure to these agents in vivo.

Animals↗
PubMed1989

Cell cycle regulation of H2b histone octamer DNA-binding activity in Chinese hamster lung fibroblasts.

The promoter regions of H2b histone genes contain a 14-base-pair element which includes the octamer ATTTGCAT. Mutational analysis has implicated the octamer element in the cell cycle-dependent expression of H2b histone genes. In this report, we address the question of whether the DNA-binding activity of the octamer transcription factor is itself cell cycle regulated. By using a gel mobility shift assay, we measured the relative amounts of octamer-binding activity during various phases of the cell cycle in serum-synchronized Chinese hamster fibroblasts. We found that the activity increased approximately fivefold between late G1 phase and early S phase and then decreased threefold between late S phase and G2 phase. These cell cycle-dependent changes in octamer DNA-binding activity may in part account for the selective transcription of H2b histone genes in late G1 and S phases.

Animals↗
PubMedDate not supplied

Molecular cloning of G1 phase mRNAs from a subtractive G1 phase cDNA library.

Many G1-phase-specific mRNAs have been identified from various normal or transformed cells based on serum induction and re-entry into the cell cycle from quiescence. However, these mRNAs may not represent some important genes expressed during G1 phase in continuously cycling cells. The eukaryotic cell cycle possesses two cdk (cyclin-dependent kinase) dependent regulatory gates through which cells pass during late G1 phase and G2 phase of each cycle. Subtractive hybridization was employed to synthesize a high R0t fraction cDNA library enriched in sequences expressed during G1 phase prior to passage through the G1-phase gate. To prepare G1-phase cells from continuously cycling cell populations, G1-phase HeLa cells were collected by centrifugal elutriation and highly synchronous S phase cells were obtained by double thymidine block followed by centrifugal elutriation. A G1-phase subtractive cDNA library was prepared by subtracting G1-phase cDNA with a 10-fold excess of S-phase mRNA. Single-stranded, G1-phase cDNAs were isolated by oligo(dA) chromatography. The library was screened with a high R0t fraction subtractive probe population. Following two rounds of screening, 20 positive clones were obtained. Northern blot analysis indicated that six of these clones were enhanced in expression level during G1 phase when compared with S phase. Nucleotide sequence comparison of each clone with the GenBank data base revealed that hG1.11 was highly homologous (99%) to the apoferritin light chain gene and clones hG1.6, hG1.10, hG1.17, and hG1.18 represented new G1-phase-enriched members of four human ribosomal protein gene families (71-95% homology). The last clone, hG1.1, encoded a highly charged polypeptide not previously identified. Additional study of these G1-phase-enriched mRNAs will be required to determine their role in cell cycle progression and the G1-phase gateway through which cells transit as they proceed through the cell cycle.

Actins↗
PubMed2004

Interferon-alpha: regulatory effects on cell cycle and angiogenesis.

In the current study, we investigated the effects of interferon-alpha (IFN-alpha) on proliferation and angiogenesis in neuroendocrine tumor disease. Using a panel of human neuroendocrine tumor cell lines, we confirmed functionally active IFN-alpha signaling by STAT activation and nuclear translocation as well as transactivation. IFN-alpha results in anchorage-dependent and -independent growth inhibition due to a delayed progression from S-phase to G2 phase of the cell cycle. This was due to substantial reduction in cellular cyclin B levels resulting in the inhibition of Cdc2 kinase activity. In parallel to growth inhibition, we observed a profound inhibition of VEGF gene transcription by IFN-alpha in human neuroendocrine tumor cells due to an Sp1/Sp3-dependent inhibition of VEGF promoter activity. Treatment of neuroendocrine tumors with IFN-alpha in nude mice resulted in growth inhibition and inhibition of angiogenesis. Furthermore, treatment of neuroendocrine tumor patients with IFN-alpha resulted in decreased VEGF expression as well as tumor angiogenesis in liver metastases. In summary, IFN-alpha acts via direct antiproliferative effects as well as inhibition of tumor angiogenesis mediated by suppression of VEGF gene expression in neuroendocrine tumor disease.

Angiogenesis Inhibitors↗
PubMed2006

CHK1 phosphorylates CDC25B during the cell cycle in the absence of DNA damage.

CDC25B is one of the three human phosphatases that activate the CDK-cyclin complexes, thereby triggering cell-cycle progression and division. Commitment to early mitotic events depends on the activation of a centrosomal pool of CDK1-cyclin-B1, and CDC25B is thought to be involved in initiating this centrosomal CDK1-cyclin-B1 activity. Centrosome-associated checkpoint kinase 1 (CHK1) has been proposed to contribute to the proper timing of a normal cell division cycle by inhibiting the activation of the centrosomal pool of CDK1. Here, we show that CDC25B is phosphorylated by CHK1 in vitro on multiple residues, including S230 and S563. We demonstrate these phosphorylations occur in vivo and that they are dependent on CHK1 activity. S230 CHK1-mediated phosphorylation is detected in cell extracts during S phase and G2 phase in the absence of DNA damage. We show that the S230-phosphorylated form of CDC25B is located at the centrosome from early S phase until mitosis. Furthermore, mutation of S230 to alanine increases the mitotic-inducing activity of CDC25B. Our results support a model in which, under normal cell cycle conditions and in the absence of DNA damage, CHK1 constitutively phosphorylates CDC25B during interphase and thus prevents the premature initiation of mitosis by negatively regulating the activity of CDC25B at the centrosome.

Amino Acid Sequence↗
PubMed1992

The role of primer recognition proteins in DNA replication: inhibition of cellular proliferation by antisense oligodeoxyribonucleotides.

Primer recognition proteins (PRP) are cofactors for DNA polymerase alpha and may have a role in lagging-strand DNA replication. PRP is composed of two subunits, which we have previously identified as the protein-tyrosine kinase substrate annexin II and phosphoglycerate kinase (PGK). In this study, we have examined the physiological involvement of these proteins in DNA synthesis and cell proliferation. When exponentially growing human HeLa cells are exposed to antisense phosphorothioate oligodeoxynucleotides to annexin II, ongoing DNA synthesis is reduced. The extent of reduction with antisense oligodeoxynucleotide to PGK was much less than with the antisense annexin II oligodeoxynucleotide. Reductions in the labeling and mitotic indices of HeLa cell cultures are seen after exposure to antisense oligodeoxynucleotides. Flow cytometric analyses indicate that progression from S phase to G2 phase of the cycle is retarded by exposure of cells to the antisense oligodeoxynucleotides. Corresponding sense oligodeoxynucleotides have no inhibitory effects on these parameters. The new synthesis of annexin II and PGK is specifically reduced in the presence of antisense oligodeoxynucleotides, indicating that the complex of newly synthesized annexin II and PGK may participate in PRP function. These experiments indicate that annexin II and PGK may have a physiological role in DNA synthesis and cell cycle progression, and represent the first physiological role for annexin II monomer in cells.

Annexins↗
PubMed1980

Studies on antitumor activity of prumycin. III. Mode of action of prumycin on HeLa S-3 cells.

The mode of action of prumycin was investigated using synchronized and asynchronous cultured HeLa S-3 cells. Prumycin inhibited significantly the growth of HeLa S-3 cells at the concentration over 5 mcg/ml. DNA synthesis as well as protein synthesis was strongly inhibited at the concentration of 10 mcg/ml of prumycin, but RNA synthesis was not inhibited by the same concentration. Prumycin did not block the transition of the cells from M phase to G1 phase, however, G2 phase cells were blocked clearly by this antibiotic.

Amino Sugars↗
PubMed2000

[Angiocentric T-cell lymphoma]

SUMMARY: The CD20+ variant of angiocentric T-cell lymphoma is an unusual type of T-cell lymphomas that present cystic changes in organs because of ischaemic necroses. The purpose of this study was to describe a case of CD20+angiocentric T-cell lymphoma, discussing its clinical, histopathological and immunohistochemical features, to analyze its proliferation kinetics and to consider its possible relationship to the Epstein-Barr virus (EBV) to understand better the pathobiological nature of the disease. METHODS: The clinical, histopathological, immunohistochemical and single-cell DNA cytophotometric features of the case were analyzed. In addition in situ hybridization was performed to detect EBV. RESULTS: The 24 years old woman was admitted to our Institute because of pain in the abdominal region and weight loss. There were enlarged lymph nodes on the neck, and biopsy was done. Histological diagnosis: angiocentric T-cell lymphoma, CD20+ variant. CD3, CD43, CD45RA and CD45R0 antigens were positive in the atypic lymphoid cells of the tumour and in cells infiltrating the vascular wall. DNA index was 0.8589 (hypodiploid). Tumour cells in G1 phase: 47%, S phase: 45.4%, G2 phase: 7.6%. Combined chemotherapy was administered because of clinical stadium IV/B of malignant lymphoma (5 CHOP-Bleo, CEPP, CEP, CMVE treatment). The disease showed gradual progression and the patient died 14 months after the first symptoms had appeared. CONCLUSIONS: In the last 13 years there were 5 cases of angiocentric T-cell lymphoma at our Institute. The CD20+ variant is rare, its clinical symptoms are special, the prognosis is unfavourable. The cause why we demonstrate this case is to call attention to a new treatment for these patients by immunotherapy using monoclonal antibodies against CD20 antigen.

Journal Article↗
PubMed1999

Suppression of apoptosis does not foster neoplastic growth in Barrett's esophagus.

Esophageal adenocarcinoma often arises in association with metaplastic and dysplastic mucosa in Barrett's esophagus. Derangements in cell cycle control and apoptosis regulation might be responsible for the progression from metaplasia to dysplasia and adenocarcinoma We tested this hypothesis by performing cell cycle analysis, in situ detection of apoptosis, and evaluation for the immunohistochemical expression of proteins involved in proliferation (Ki-67), the control of apoptosis (bcl-2, bcl-x and bax), and cell cycle regulation (retinoblastoma and cyclin D1). We studied 17 randomly selected paraffin-embedded esophagectomy specimens that contained intestinal metaplasia without dysplasia, low-grade dysplasia, high-grade dysplasia, and esophageal adenocarcinoma Compared with gastric controls and intestinal metaplasia without dysplasia, high-grade dysplasia and esophageal adenocarcinoma demonstrated greater numbers of cells in S phase and G2 phase. Comparison of the proliferation index and the apoptotic rate in intestinal metaplasia without dysplasia, low-grade dysplasia, high-grade dysplasia, and esophageal adenocarcinoma showed a statistically significant trend that linked an increasing proliferation index and apoptotic rate with increasing histologic severity (P = .006 and P = .0002, respectively). A statistically significant linear association was found between bcl-x expression, bax expression, and the bcl-2-to-bax expression ratio versus increasing histologic severity (P = .0004, P = .007, and P = .03, respectively). These data support the hypothesis that neoplastic transformation of intestinal metaplastic epithelium in the esophagus might result from sequential changes in the expression of proteins involved in the control of apoptosis and the cell cycle. Furthermore, suppression of apoptosis does not seem to foster neoplastic growth in Barrett's esophagus. These observations will lead to a better understanding of the pathogenesis of esophageal adenocarcinoma and might contribute to enhancing the diagnostic accuracy when presented with dysplastic lesions.

Adenocarcinoma↗
PubMed2003

[A cyclin A-like protein is localized in the cells of Physarum polycephalum and functions in the cell cycle].

The subcellular distribution of a Cyclin A-like protein in the cells of Physarum polycephalum and the function of the protein in the cell cycle were studied by immunoelectron microscope and anti-Cyclin A antibody blocking. After labeled with an anti-Cyclin A monoclonal antibody, the density of gold particles in the labeled specimens was much higher than that in the control, indicating that a Cyclin A-like protein existed in Physarum polycephalum. In the labeled specimen, the gold particles density of the nucleus was higher than that of cytoplasm, which was similar to that of the control, demonstrating that the Cyclin A-like protein was a nuclear protein. The gold particles density of the nuclei varied during the cell cycle. The highest appeared in S phase and the lowest came in metaphase and ana-telophase, which was close to that in the control. From S phase to metaphase, the gold particle densities dropped down gradually. The changes in the gold particle density showed the changes in the content of the Cyclin A-like protein. After treated with the anti-Cyclin A antibody in S phase and G2 phase respectively, the nuclei of Physarum polycephalum were arrested in the phases and the morphology of these nuclei became irregular. When treated with the anti-Cyclin A antibody in prophase, the nuclei appeared abnormal. These results suggested that the Cyclin A-like protein is important in cell cycle regulation of Physarum polycephalum, essentially in S/G2 and G2/M changes.

Animals↗
PubMed2005

[In vitro study of the directed inducing cartilage cells from rat bone mesenchymal stem cells on scaffolds].

This study was conducted to assess the cell proliferation and cell cycle of the directed inducing cartilage cells from rat bone mesenchymal stem cells on collagen sponge and compare the results with those of the plane inducing cartilage cells. The MSCs were isolated from rat bone marrow by density gradient centrifuge and adhesive property, and then were induced into chondrogenic differentiation by adding transforming growth factor-beta1 (TGF-beta1), dexamethasone, transferring and insulin on collage sponge and plane condition. Immunohistochemistry was applied to detect the expression of collagen type II on the scaffolds and plane conditions. The cell proliferation and cell cycle on different conditions were detected with MTT automated colormetric microassay and flow cytometry. The differentiation of MSCs toward chondrogenic phenotype was verified by the positive result of collagen type II on the scaffolds and plane condition. The cell viability in scaffolds was better than that in plane conditions. The S phase and G2 phase were 30 percent in whole cell cycle on the scaffold, which was different from that of the control groups. The method of using the Using directed inducing cartilage from bone MSCs combined with collage sponge to construct tissue-engineered cartilage is feasible; it is better than the method of plane directed inducing.

Animals↗
PubMed2006

[Reconstructing the JAK/STATs signal pathway restored the anti-proliferative response of MHCC97 on interferon alpha].

OBJECTIVE: To elucidate the roles of JAK/STATs signal pathway on anti-proliferative effects induced by IFN-alpha in MHCC97. METHODS: An IRF9 expression vector was transfected into MHCC97 with Dosper. The expression of IRF9, cycle regulating proteins and the forming of ISGF3 complex were detected using Western blot and EMSA, respectively. Cell proliferation and distribution were monitored using MTT and flow cytometry. RESULTS: High expression of IRF9 restored the anti-proliferative response of MHCC97 on IFN-alpha treatment and delayed the cell transition from S phase to G2 phase induced by IFN-alpha. CONCLUSION: The integrity and functions of JAK/STATs signal pathway played an important role in mediating the anti-proliferative effects of IFN-alpha in MHCC97.

Carcinoma, Hepatocellular↗
PubMed2006

[Inducement effect of recombinant human TNF-alpha on apoptosis of breast cancer cell line ZR75-1 and Its mechanism].

BACKGROUND & OBJECTIVE: Tumor necrosis factor alpha (TNF-alpha) is an important agent for tumor biotherapy because of its strong antitumor activity, but its clinical application is limited because of its severe fatal systemic toxicity. A new recombinant human (rh) mutein, mutant type (mt) 471rhTNF-alpha, was produced to decrease toxicity while keep antitumor activity of wild type (wt) TNF-alpha. This study was to compare the antitumor activities of mt-471rhTNF-alpha and wt-rhTNF-alpha, and analyze the mechanism of tumor cell apoptosis induced by mt-471rhTNF-alpha. METHODS: Breast cancer cell line ZR75-1 was treated with 100 microg/L of mt-471rhTNF-alpha or wt-rhTNF-alpha for 12 h. Cell apoptosis was analyzed with 2% agarose gel electrophoresis, and cell cycle distribution was analyzed by flow cytometry. The activation of nuclear factor-kappaB (NF-kappaB) p65 in ZR75-1 cells treated with 10 microg/L, 50 microg/L, and 100 microg/L of mt-471rhTNF-alpha or wt-rhTNF-alpha for 4 h were detected using Trans AMTM NF-kappaB p65 kit based on ELISA. RESULTS: ZR75-1 cells treated with mt-471rhTNF-alpha had typical ladders of DNA fragmentation, whereas ZR75-1 cells treated with wt-rhTNF-alpha only had weak ladders; the apoptosis rate of ZR75-1 cells was significantly higher in mt-471rhTNF-alpha group than in wt-rhTNF-alpha group [(44.6+/-3.6)% vs. (24.7+/-2.7)%, P<0.05]. The proportion of G1 phase cells was significantly higher in mt-471rhTNF-alpha group than in control group and wt-rhTNF-alpha group [(66.6+/-4.2)% vs. (34.8+/-3.1)% and (46.2+/-3.8)%, P<0.05]; the proportions of S phase and G2 phase cells were significantly lower in mt-471rhTNF-alpha group than in control group and wt-rhTNF-alpha group [(33.2+/-2.9)% vs. (50.1+/-3.8)% and (45.7+/-2.9)%, P<0.05; (0.2+/-0.0)% vs. (15.1+/-2.2)% and (8.1+/-3.1)%, P<0.05]. When treated with 50 microg/L rhTNF-alpha for 4 h, NF-kappaB activation was significantly higher in wt-rhTNF-alpha group than in mt-471rhTNF-alpha group (3.3+/-0.1 vs. 1.5+/-0.2, P<0.05 ). CONCLUSIONS: The antitumor ability of mt-471rhTNF-alpha is more stronger than that of wt-rhTNF-alpha. The explanation for the enhanced apoptosis-inducible ability of mt-471rhTNF-alpha could be that NF-kappaB activation is inhibited in tumor cells treated with mt-471rhTNF-alpha.

Apoptosis↗
PubMed1976

Pulse cytophotometric analysis of cell cycle perturbation with bleomycin in vitro.

The kinetic response of a human lymphoma cell line to bleomycin has been analyzed, using an ICP-11 pulse cytophotometer. Bleomycin induced a delay of the cell-cycle traverse in G2 phase, the extent and recovery of which depended on drug concentration, exposure time, and cell cycle stage where treatment was applied. Different phase sensitivity for lethal damage (G2 phase) and kinetic response (early S phase) were documented. Recovery from G2 block did not predict for unimpaired reproductive capacity.

Bleomycin↗
PubMed1981

The effects of inhibitors of DNA biosynthesis on the cytotoxicity of 6-thioguanine.

The effects of several metabolic inhibitors of DNA synthesis on the antiproliferative activity of 6-thioguanine (6-TG) were examined using cultured L1210 leukemia cels. The presence of hydroxyurea (HU), 1-beta-D-arabinofuranosylcytosine (araC), or 5-fluorodeoxyuridine (FUdR) in cultures of L1210 leukemic cells during exposure of 6-TG did not increase the degree of inhibition of cellular replication produced by the 6-thiopurine, but instead partially protected cells against the delayed cytotoxicity of 6-TG, implying that DNA replication was essential for the expression of cytotoxicity by the purine antimetabolite. Consistent with these results was the finding that synchronized L1210 cells exposed to 6-TG were the most susceptible to the cytotoxic action of the 6-thiopurine during G1/S and S phase. However, G2 phase cells were also sensitive to 6-TG indicating that at least two metabolic lesions are responsible for the production of cytotoxicity. Alkaline sucrose gradient sedimentation of L1210 cells exposed to 6-TG revealed that the purine analog causes structural changes in DNA suggesting that these hitherto unreported lesions may be involved in the cytotoxicity caused by this agent.

Animals↗
PubMed1996

Radiosensitivity, apoptosis and repair of DNA double-strand breaks in radiation-sensitive Chinese hamster ovary cell mutants treated at different dose rates.

The relationship of cell survival to induction and repair of DNA double-strand breaks (DSBs), as assessed by the neutral comet assay, was studied in two pairs of CHO cell lines, repair-deficient mutants xrs-5-11 and V3, and their respective parent lines K-1 and AA8, treated at two dose rates, 10.5 and 0.09 Gy/min. A marked difference in cell survival after irradiation was found between each pair of lines. For initial DNA damage, there was a significant difference between each pair of lines after the low-dose-rate treatment but not with high-dose-rate irradiation. Initial DSBs were dependent on dose at both dose rates. When residual damage at 2 h after irradiation was assessed, the 5-11 cells showed significantly more damage than K-1 cells after both high- and low-dose-rate irradiation. The V3 cells also showed more residual damage than the AA8 cells, but this difference was significant only after high-dose-rate irradiation. The results indicate that low-dose-rate irradiation can differentiate better between the DSB rejoining capacity of the sensitive and resistant cells and are consistent with the idea that it is the slow component of repair of DSBs which is different between them. Further studies with 5-11 and K-1 cells showed that radiation-induced apoptosis was dependent on dose, with a higher fraction of apoptotic cells in 5-11 than in K-1 cells after exposure to a given high-dose-rate radiation dose. However, the levels and time course of induction of apoptosis were similar for doses which gave equal levels of clonogenic survival. Radiation treatment was found to delay the progression of 5-11 and K-1 cells through the cell cycle to the same extent, with accumulation of cells in S phase and G2 phase, at 4 and 12 h after irradiation, respectively. There was no evidence for a G1-phase arrest. Western blotting revealed that there were higher levels of p53 and Waf1 protein in nonirradiated 5-11 than in K-1 cells, and that a dose of 5 Gy of high-dose-rate radiation up-regulated the expression of p53 and Waf1 protein to similar levels in both cell lines. There was no change in levels of the Gadd45 and Bcl2 proteins in either cell line after irradiation. These results suggest that the accumulation of p53 and Waf1 protein does not cause early G1-phase arrest in these cells.

Animals↗