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71.
C.D. Hassall A.J. Gandolfi R.C. Duhamel K. Brendel 《Chemico-biological interactions》1984,49(3):283-297
The nephrotoxicity of chlorotrifluoroethylene (CTFE) was examined using isolated rabbit renal tubules suspensions. Exposure of the tubules to CTFE resulted in consumption of CTFE, formation of a glutathione conjugate and inhibition of active organic acid transport. Synthetic cysteine, N-acetylcysteine or glutathione conjugates of CTFE inhibited transport indicating S-conjugation as a possible toxic pathway. 1,2-dichlorovinyl glutathione (DCVG), a model synthetic glutathione conjugate, was used to examine the degradation and toxicity of these conjugates. DCVG inhibited rabbit renal tubule transport in vivo and in vitro. The DCVG was found to be degraded with the evolution of glutamine and glycine to produce the ultimate nephrotoxicant, dichlorovinyl cysteine. Dichlorovinyl cysteine is then bioactivated with the release of ammonia. This sequential degradation explains the latency of DCVG-induced renal transport inhibition relative to dichlorovinyl cysteine. It is now evident that certain halogenated ethylenes are capable of being biotransformed to glutathione conjugates in the kidney with their subsequent hydrolysis to nephrotoxic cysteine conjugates. 相似文献
72.
Biochemical significance of enhanced activity of fluorinated 1,25-dihydroxyvitamin D3 in human cultured cell lines 总被引:1,自引:0,他引:1
Several human cancer cells possess receptors for 1,25-dihydroxyvitamin D3[1,25-(OH)2D3]. In these cells 1,25-(OH)2D3 has a biphasic concentration-dependent regulatory effect on cell replication and specifically induces its own metabolism. We have studied the effects on these parameters of the native hormone together with those of two analogues fluorinated at the 24-carbon and of 1,24R,25-trihydroxyvitamin D3[1,24R,25-(OH)3D3]. The difluorinated analogue 24,24-difluoro-1,25-(OH)2D3[24,24-F2-1,25-(OH)2D3] is an approximately fivefold more potent inhibitor of cellular replication than the native hormone, while 1,24R,25-(OH)3D3 is about fivefold less potent. This enhanced potency of the fluorinated analogue parallels its enhanced potency in in vivo studies of its effects on calcium and mineral metabolism. However, although the analogue retains replication stimulatory activity, it is clearly no more potent than the native hormone in this activity: 1,24R,25-(OH)3D3 has no significant stimulatory activity. Exposure of the cells to 1,25-(OH)2D3 at 0.05 nM for 6 h increases the subsequent conversion of labelled hormone to aqueous phase soluble compounds by 6.7-fold. None of the other compounds had a similar effect at this concentration. At 10 nM all 1-hydroxylated compounds increased aqueous phase radioactivity about equally (13 to 17-fold); this effect is still specific since 25-OH D3 had no such effect even at 10 nM. Studies on the effects of the fluorinated analogues upon receptor binding of hormone in cell cytosols and uptake of hormone by intact cells clearly demonstrate that the enhanced activity of these analogues is not due to higher receptor affinity or more rapid access to intracellular receptor.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
73.
Summary H1° histones were purified by preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis from human lung carcinoma (line DMS79), human hepatoblastoma (HepG2), human adult lung and human adult and fetal liver. The purified human H1° histones were analyzed for their amino acid composition and terminal residues. The comparative analysis of the amino acid compositions of the different human H1° histones showed that: (a) all the H1° preparations have the characteristically high lysine content associated with a low arginine content, which distinguishes outer histones from core histones; (b) H1° is distinguishable from other H1 histones by the presence of methionine and histidine; (c) H1° histones from human adult, fetal and cancer cells are very similar in amino acid composition, and in cancer cells the level of the H1° histone is not inversely related with cell growth rate nor with the expression of the -fetoprotein gene. 相似文献
74.
Summary We describe the in vitro influence of 3,5,3′-triiodo-l-thyronine (T3),l-thyroxine (T4), a thyroid-stimulating hormone (TSH), and/or estradiol (E2: chosen as the control of the methodology) on the cell kinetics (cell distribution in the S+G2+M phases) of mouse MXT and human MCF-7 mammary cancer cells. Experiments were performed by means of a cell image processor,
analyzing MCF-7 or MXT cells that had been grown on glass cover slips and whose nuclei had been stained by the Feulgen reaction,
which is selective and quantitative (stoichiometric) with respect to DNA. We show that T3, T4, and TSH at 0.01 μM dramatically stimulate the cell kinetics of the MXT mouse and the MCF-7 human mammary cancer cell lines. Indeed, the three
hormones bring about a significant transient increase in the S+G2+M fraction as does E2. Furthermore, our data indicate that E2 and TSH are antagonistic with regards to MXT or MCF-7 cell kinetics.
This work is supported by grants awarded by the IRSIA and the Fonds de la Recherche Scientifique Médicale (FRSM, Belgium). 相似文献
75.
Metastasis is a major, life-threatening complication of cancer. The bloodstream is the most important disseminative route
for cancer cells liberated from their parent tumors. Single circulating cancer cells are arrested in the microvasculature,
where the vast majority are killed by rapid or slow processes, and the relatively few survivors grow into micrometastases.
We review the underlying causes of one type of rapid cancer cell death in the microcirculation, namely, that caused by biomechanical
interactions of cancer cells with microvessel walls, which may result in cell surface membrane expansion and lethal rupture.
These lethal interactions appear to be important rate-regulators in hematogenous metastasis, and to dictate some aspects of
metastatic patterns. Although these are not the only interactions involving cancer cells, in contrast to others involving
cellular and humoral defense mechanisms, they have received comparatively little attention. 相似文献
76.
Ras interaction with the GTPase-activating protein (GAP) 总被引:18,自引:0,他引:18
M D Schaber V M Garsky D Boylan W S Hill E M Scolnick M S Marshall I S Sigal J B Gibbs 《Proteins》1989,6(3):306-315
Biologically active forms of Ras complexed to GTP can bind to the GTPase-activating protein (GAP), which has been implicated as possible target of Ras in mammalian cells. In order to study the structural features of Ras required for this interaction, we have evaluated a series of mutant ras proteins for the ability to bind GAP and a series of Ras peptides for the ability to interfere with this interaction. Point mutations in the putative effector region of Ras (residues 32-40) that inhibit biological activity also impair Ras binding to GAP. An apparent exception is the Thr to Ser substitution at residue 35; [Ser-35]Ras binds to GAP as effectively as wild-type Ras even though this mutant is biologically weak in both mammalian and S. cerevisiae cells. In vitro, [Ser-35]Ras can also efficiently stimulate the S. cerevisiae target of Ras, adenylyl cyclase, indicating that other factors may influence Ras/protein interactions in vivo. Peptides having Ras residues 17-44 and 17-32 competed with the binding of Ras to E. coli-expressed GAP with IC50 values of 2.4 and 0.9 microM, respectively, whereas Ras peptide 17-26 was without effect up to 400 microM. A related peptide from the yeast GTP-binding protein YPT1 analogous to Ras peptide 17-32 competed with an IC50 value of 19 microM even though the YPT1 protein itself is unable to bind to GAP. These results suggest that determinants within Ras peptide 17-32 may be important for Ras binding to GAP. 相似文献
77.
Teresa L. Johnson Mary Pat Moyer 《In vitro cellular & developmental biology. Plant》1990,26(11):1095-1100
Summary Normal human colon mucosa cells and cells obtained from histologically normal tissues near that cancer were fused with human
colon cancer cells. Resultant hybrid populations of normal and malignant cell fusions behaved as nonmalignant cells in culture,
were unable to grow in soft agar, did not express tumor-associated antigens, and were nontumorigenic in nude mice. Autofusion
of the cancer cell population led to a phenotype intermediate between normal and malignant cells. That is, the cultures had
a much lower plating efficiency in soft agar, and the tumors had a longer latency and slower growth rate in nude mice. This
is the first cell culture system to demonstrate that normal epithelial cells can suppress malignancy of their autologous cancer
cells, and is a prelude to more extensive studies of genetic events involved in malignant conversion of human colonic epithelium.
This study was supported by The University of Texas Health Science Center at San Antonio Center for Human Cell Biotechnology
and a graduate student stipend (T. J.) from the Department of Cellular and Structural Biology. 相似文献
78.
Rolando Campos Argelia Garrido Ricardo Guerra Alfonso Valenzuela 《Free radical research》1990,10(4):259-264
Reperfusion of rat kidney submitted to temporal ischaemia induces a decrease in glutathione content. Lipid peroxidation is not detected in kidney homogenates but microsomes obtained after periods of reperfusion longer than 60 minutes show increased malondialdehyde values correlated with high oxygen consumption and superoxide free radical generation. Microsomes obtained from kidneys submitted to 15 or 60 minutes of reperfusion are resistant to NADPH-induced lipid peroxidation but after 120 minutes of reperfusion an increased lipid peroxidative response is observed. Although the mechanism of the protection found in microsomes against the induction of oxidative stress in the first 60 minutes of reperfusion is unknown, it is postulated that this subcellular fraction plays an important role in the oxidative stress observed after longer periods of reperfusion. 相似文献
79.
Effects of interleukin-12 on in vitro culture with interleukin-2 of regional lymph node lymphocytes from lung cancer patients 总被引:2,自引:0,他引:2
T. Hanagiri Mitsuhiro Takenoyama Takashi Yoshimatsu Chikashi Hirashima Ichiro Yoshino Kozo Nakanishi Akira Nagashima Kikuo Nomoto Kosei Yasumoto 《Cancer immunology, immunotherapy : CII》1996,43(2):87-93
In the present study, we carried out a functional analysis of regional lymph node lymphocytes (RLNL) from patients with lung
cancer after in vitro activation by interleukin-2 (IL-2) and interleukin-12 (IL-12). IL-12 (100 U/ml) enhanced both the proliferation
and cytotoxic activity of RLNL in a culture with low doses of IL-2 (5 – 10 JRU/ml). After comparing an RLNL culture with a
low dose of IL-2 alone, a higher proportion of CD8+ cells and CD56+ cells and a lower proportion of CD4+ cells were found in the culture with both IL-12 and a low dose of IL-2. Such a combination of the cytokines effectively activated
RLNL in terms of the expression of IL-2 receptors. In the culture condition of IL-12 and a low dose of IL-2, a synergistic
effect was observed in the production of such cytokines as interferon γ, tumor necrosis factor α (TNFα), and TNFβ, as well
as in tumor cytotoxicity. However, the addition of IL-12 inhibited the cytotoxicity of RLNL in the culture with a high dose
of IL-2 (100 JRU/ml). This inhibition is considered to be partially due to the endogenous production of TNFα by lymphocytes,
because the neutralization of TNFα bioactivity partially restored the cytotoxic activities of RLNL. Furthermore, in the presence
of hydrocortisone, IL-12 synergistically enhanced the cytotoxic activity of RLNL cultured with a high dose of IL-2. These
results provide useful information about the improvement of adoptive immunotherapy against cancer using RLNL.
Received: 2 February 1996 / Accepted: 30 July 1996 相似文献
80.
Elizabeth A. Kingsley Teresa E. Carter Kevin D. Barrow Pamela J. Russell 《Cancer immunology, immunotherapy : CII》1996,41(6):348-354
A monoclonal antibody, BLCA-8, was raised against the human bladder cancer cell line, UCRU-BL-17CL. By flow cytometry and immunoperoxidase staining, this antibody was found to possess high specificity for bladder tumours, some reactivity with fetal tissues, and no reactivity with normal bladder, or any normal or malignant tissue. This high specificity and the stability of the antigen to the urinary environment suggest that BLCA-8 may have potential for use as an anti-bladder-cancer therapeutic agent. By thin-layer chromatography and autoradiography, BLCA-8 was found to bind four components within the neutral lipid fraction of a bladder cancer cell line, UCRU-BL-17/23. These components hadR
F values of 0.22, 0.16/0.15 (doublet), 0.12 and 0.08, and migrated below globoside, indicating the presence of more than four sugars. By enzyme-linked immunosorbant assay and thin-layer chromatography it was found that the binding of BLCA-8 to the lipid extract was increased by both mild alkaline hydrolysis and enzymatic treatments, indicating that adjacent phospholipids and glycolipids interfere with the accessibility of the antibody-binding site. Full biochemical characterisation of the BLCA-8 antigen is currently underway. 相似文献