摘要:

AbstractThis study reports that exposure of endothelial cells [bovine aortic endothelial cells (BAEC) and porcine aortic endothelial cells (PAEC)] to ionizing radiation leads to activation of the basic fibroblast growth factor (bFGF) and platelet‐derived growth factor (PDGF)‐B genes. Nuclear RNA run‐on experiments showed an increase in nuclear RNA of these factors within 90 min after delivery of a dose of 4 Gy. In addition, there was a dose‐and time‐dependent transient increase in bFGF and PDGF‐B mRNA transcripts, although there were differences in the kinetics of these responses between BAEC and PAEC. Radiation‐induced activation of the bFGF and PDGF‐B genes was also manifested by secretion of the corresponding proteins into the culture media of the irradiated endothelial cells. In contrast, the acidic fibroblast growth factor (aFGF), PDGF‐A, and transforming growth factor beta (TGFβ) genes were not concomitantly activated in these cells, as indicated by lack of increase in their mRNA levels. Activation of specific growth factor genes and the extracellular secretion of their products may play an important role in modulating the radidation response via autocrine or paracrine mechanisms. © 1

ISSN:1065-7541    

DOI:10.1002/roi.2970030102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractWe investigated the effect of overexpression of the gene for gamma‐glutamyltranspeptidase (GGTP) on the gamma irradiation sensitivity of human bronchoepithelial cell line IB3–1 or A549 lung carcinoma cells. The enzyme has been considered a putative radioprotector because it is the only enzyme capable of degrading extracellular glutathione to ultimately provide cysteine for resynthesis of intracellular glutathione. Clonal sublines of each cell line were isolated after transfection with a plasmid containing both the rat GGTP cDNA and neorgene, and selected in G418. Each transfected clone demonstrated a different degree of GGTP enzymatic expression by biochemical analysis. The D0of parent IB3–1 cells was 1.434 ± 0.138 Gy, n 2.331 ± 0.685, and was unchanged by GGTP overexpression, D01.932 ± 0.690 Gy (P = 0.133), n 2.916 ± 2.7 (P = 0.628). In contrast, overexpression of the MnSOD transgene in IB3–1 cells increase the shoulder on the irradiation survival curve for IB3–1 cells, showing significant increase in the shoulder, D01.239 ± 0.1 Gy (P = 0.079), n 7.276 ± 0.1 (P<0.001). Lung cancer cell line A549 was subcloned after expression of the GGTP transgene, and clonal subline 22 demonstrated stably increased GGTP activity and protein production by Western analysis. The parental A549 line was also redoned by limiting dilution. A series of clonal sublines of clonal line 22 expressed up to a 97‐fold increase in GGTP expression compared to control clones. In clonogenic cell survival assays in the presence or absence of added glutathione, no difference in irradiation sensitivity was detected between parent or GGTP transfected and overexpressing subclones despite an increase in GGTP activity. The D0of the subclone 10 of parent A549 cells was 1.6 ± 0.40 Gy and n was 4.8 ± 3.0, α 0.13 ± 0.10, β 0.052 ± 0.02; while the D0for GGTP overexpressing clone 17, a subclone of line 22, was 1.3 ± 0.05 Gy, n 2.6 ± 0.18, a 0.279 ± 0.01, p 0.059 ± 0.01. The cell lines were not significantly different with respect to D0(P = 0.55), indicating no significant effect of GGTP overexpression on radiosensitivity. Thus, GGTP overexpression in either normal lung bronchoalveolar cell line IB3–1 or lung cancer cell line A549 does not induce radioresistance in

ISSN:1065-7541    

DOI:10.1002/roi.2970030103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractTo examine the dependence on exposure rate of killing and mutagenesis by γ‐rays, two lines of Chinese hamster cells were studied. V79 cells were used to induce 6‐thioguanine resistance (6‐TGr) due to a mutation of the constitutive gene hypoxanthine‐guanine phosphoribosyl transferase (hgprt). Mutation of the bacterial geneguanine phosphoribosyl transferase (gpt) was studied in a line of mutated CHO cells,hgprt—which carried a single copy of gpt—by scoring cells that became 6‐TGr. The purpose of the study was to determine if the induction of either the mutant phenotypes or genotypes depended on dose rate, i.e., presumably were influenced by repair. To simulate a cell‐renewal population of cells in vivo, low enough dose rates of γ‐rays were used which permitted essentially continuous growth for 50–100 doublings in cell number. Considerable repair of mutagenesis as well as lethality was evident. Compared to exposures at high‐dose‐rate, the decreased frequency of mutants at low‐dose‐rate appeared to be accompanied by a shift in genotype toward that of unexposed cells, i.e., in a shift toward a higher frequency of intragenic mutations than was observed with high‐dose‐rate

ISSN:1065-7541    

DOI:10.1002/roi.2970030104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractEstramustine, a conjugate of estradiol and nitrogen mustard, has been shown previously to depolymerize microtubules, inhibiting the formation of mitotic spindles and arresting cells in G2/M. Estramustine at concentrations of 10–30 μM inhibited the growth of EMT6 mouse breast carcinoma cells in a concentration‐dependent fashion. The viability (clonogenicity) of the cells also decreased as the drug concentration and exposure time increased. Pretreatment of EMT6 cells for 48 hr with 10 or 20 μM estramustine increased the radiosensitivity on EMT6 cells, producing enhancement ratios of 1.2 and 2.1, respectively. © 1995 Wiley‐L

ISSN:1065-7541    

DOI:10.1002/roi.2970030105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractIn a prospective study involving 158 patients with carcinoma of the uterine cervix, DNA content, S‐phase fraction (SPF), and Ki‐67 proliferative index were evaluated in fresh tissue using flow cytometry and immunocytochemical analysis. Of all tumors, 57.1% were aneuploid. In this subgroup, 25% of tumors had a DNA index between 1.6 and 1.8. SPF values ranged from 0.5 to 57.2% and were significantly higher (P<0.0001) in tumors with an abnormal DNA content (aneuploid). Ki‐67 labeling index ranged from 1.7 to 65.0%. No association was found between any of the above‐mentioned parameters and clinical stage or histological type of tumor. When analyzing overall survival, a statistically significant difference was found between stage IIB patients with aneuploid and diploid DNA content. In 39 carcinomas evaluated after 1 week of radiotherapy, irradiation induced a significant decrease in Ki‐67 index. In 7 aneuploid tumors where cell cycle analysis was feasible, a significant increase in G2 + M phase fraction was observed (P<0.02). We suggest these parameters are therefore useful to monitor radiation‐induced alterations in cell cycle and proliferation. © 1995 Wil

ISSN:1065-7541    

DOI:10.1002/roi.2970030106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractAcoustic pulses were detected from a patient treated by a pulsed proton radiation beam. The dose rate of the proton beam was 0.3 cGy/pulse. The signals from 100 to 700 pulses were accumulated to improve the signal to noise ratio. After accumulation, the random noise level was negligibly small compared to the signal. These results suggest the feasibility of non‐invasive monitoring of proton dose distributions in patients by sensing acoustic pulses generated during irradiation by a pulsed proton radiation beam. © 1995 Wiley‐Liss,

ISSN:1065-7541    

DOI:10.1002/roi.2970030107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

ISSN:1065-7541    

DOI:10.1002/roi.2970030108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

ISSN:1065-7541    

DOI:10.1002/roi.2970030101

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY