Biomedical subjects

T Mio

Publications and source records attributed to T Mio.

At least 55 records · Page 3Linked to original sources

PubMed1998

Human bronchial epithelial cells modulate collagen gel contraction by fibroblasts.

Connective tissue contraction is an important aspect of both normal wound healing and fibrosis. This process may contribute to small airway narrowing associated with certain airway diseases. Fibroblast-mediated contraction of a three-dimensional collagen gel has been considered a model of tissue contraction. In this study, the ability of primary cultured human bronchial epithelial cells (HBEC) obtained by bronchial brushings to modulate fibroblast gel contraction was evaluated. Human lung fibroblasts (HFL1) were cast into type I collagen gels. The gels were floated both in dishes containing a monolayer of HBEC or in dishes without HBEC. Contraction assessed by measuring the area of gels was increased at all time points from 24 h up to 96 h of coculture. At 48 h, coculture of HBEC with fibroblasts resulted in significantly more contraction than fibroblasts alone (36.6 +/- 1.2 vs. 20.4 +/- 1.7%, P < 0.05). Lipopolysaccharide (LPS, 10 micrograms/ml) stimulation of the HBEC augmented the contraction (44.9 +/- 1.0%, P < 0.05 vs. HBEC). In the presence of indomethacin, the augmentation by LPS was increased further (52.2 +/- 4.3%, P < 0.05 vs. HBEC with LPS), suggesting that prostaglandins (PGs) are present and may inhibit contraction. Consistent with this, PGE was present in HBEC-conditioned medium. Bronchial epithelial cell conditioned medium had an effect similar to coculturing. SG-150 column chromatography revealed augmentive activity between 20 and 30 kDa and inhibitory activity between 10 and 20 kDa. Measurement by enzyme-linked immunosorbent assay confirmed the presence of the active form of transforming growth factor (TGF)-beta 2. The stimulatory activity of conditioned medium was blocked by adding anti-TGF-beta antibody. These data demonstrate that, through the release of factors including TGF-beta 2 which can augment and PGE which can inhibit, HBEC can modulate fibroblast-mediated collagen gel contraction. In this manner, HBEC may modulate fibroblast activities that determine the architecture of bronchial tissue.

Animals↗

PubMed1998

Cigarette smoke extract inhibits fibroblast-mediated collagen gel contraction.

Cigarette smoking, the major cause of pulmonary emphysema, is characterized by destruction of alveolar walls. Because tissue destruction represents a balance between injury and repair, we hypothesized that cigarette smoke exposure may contribute to the development of emphysema through the inhibition of tissue contraction during the repair process. To partially evaluate this hypothesis, we investigated the effects of cigarette smoke extract (CSE) on the ability of cultured fibroblasts to mediate collagen gel contraction in vitro: CSE inhibited fibroblast-mediated gel contraction in a concentration-dependent manner (P < 0.01). Production of prostaglandin E2, a known inhibitor of fibroblast contraction, was unchanged by CSE as was cell surface integrin expression. In contrast, fibronectin production by fibroblasts was inhibited (P < 0.01), and addition of exogenous fibronectin partially restored the contractile activity, thus suggesting at least one mechanism to explain inhibition of gel contraction by CSE. When CSE was treated to remove volatile components, it showed less inhibitory activity on fibroblast-mediated gel contraction. Therefore, we also examined the effects of acrolein and acetaldehyde, two volatile components of cigarette smoke. Inhibition of contraction was observed at 5 microM acrolein and at 0.5 mM acetaldehyde. In conclusion, cigarette smoke inhibited fibroblast-mediated gel contraction, and this inhibition was due, at least in part, to the volatile components of cigarette smoke and may be mediated, at least in part, by a decrease in fibroblast fibronectin production. By inhibition of repair, these smoke components may contribute to the development of pulmonary emphysema.

Cell Survival↗

PubMed1998

Lipocortin I gene expression is higher in blood monocytes than in BAL fluid macrophages in patients with pulmonary sarcoidosis.

BACKGROUND AND AIM OF WORK: Lipocortin I, induced by corticosteroids in vivo is considered to be related to cell activation and differentiation in mononuclear phagocytes, key cells in the process of epithelioid cell granuloma formation in sarcoidosis. Therefore, we focused on the expression of lipocortin I gene in mononuclear phagocytes in patients with sarcoidosis. METHOD: The amounts of transcripts of lipocortin I gene obtained from both BAL fluid macrophages and blood monocytes were measured by RT-PCR and HPLC, and then standardized as the ratio of lipocortin I/beta-actin for comparison. RESULTS: 1. Smoking did not affect the expression of lipocortin I gene in BAL fluid macrophages and monocytes. 2. There were no differences in the amounts of expression in BAL fluid macrophages between patient groups (nonsmokers and smokers), or between patients and healthy subjects. 3. The gene expression in BAL fluid macrophages was higher than that in monocytes in patients with IPF (macrophages 1.23 +/- 0.48, vs monocytes 0.50 +/- 0.38, p < 0.05) and healthy subjects (nonsmokers: 1.66 +/- 1.17, vs 0.34 +/- 0.26, p < 0.05, smoker: 1.98 +/- 0.96, vs 0.34 +/- 0.48, p < 0.05, but sarcoidosis patients showed a higher expression of lipocortin I gene even in monocytes (2.62 +/- 1.87, vs 2.66 +/- 2.21). CONCLUSION: The increase in lipocortin I gene expression in monocytes was a disease-related finding in sarcoidosis.

Annexin A1↗

PubMed1997

Cloning of the Candida albicans homolog of Saccharomyces cerevisiae GSC1/FKS1 and its involvement in beta-1,3-glucan synthesis.

Saccharomyces cerevisiae GSC1 (also called FKS1) and GSC2 (also called FKS2) have been identified as the genes for putative catalytic subunits of beta-1,3-glucan synthase. We have cloned three Candida albicans genes, GSC1, GSL1, and GSL2, that have significant sequence homologies with S. cerevisiae GSC1/FKS1, GSC2/FKS2, and the recently identified FKSA of Aspergillus nidulans at both nucleotide and amino acid levels. Like S. cerevisiae Gsc/Fks proteins, none of the predicted products of C. albicans GSC1, GSL1, or GSL2 displayed obvious signal sequences at their N-terminal ends, but each product possessed 10 to 16 potential transmembrane helices with a relatively long cytoplasmic domain in the middle of the protein. Northern blotting demonstrated that C. albicans GSC1 and GSL1 but not GSL2 mRNAs were expressed in the growing yeast-phase cells. Three copies of GSC1 were found in the diploid genome of C. albicans CAI4. Although we could not establish the null mutation of C. albicans GSC1, disruption of two of the three GSC1 alleles decreased both GSC1 mRNA and cell wall beta-glucan levels by about 50%. The purified C. albicans beta-1,3-glucan synthase was a 210-kDa protein as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and all sequences determined with peptides obtained by lysyl endopeptidase digestion of the 210-kDa protein were found in the deduced amino acid sequence of C. albicans Gsc1p. Furthermore, the monoclonal antibody raised against the purified beta-1,3-glucan synthase specifically reacted with the 210-kDa protein and could immunoprecipitate beta-1,3-glucan synthase activity. These results demonstrate that C. albicans GSC1 is the gene for a subunit of beta-1,3-glucan synthase.

Amino Acid Sequence↗

PubMed1997

Isolation of the Candida albicans homologs of Saccharomyces cerevisiae KRE6 and SKN1: expression and physiological function.

Cell wall beta-glucan in a pathogenic fungus, Candida albicans, is highly branched with beta-1,3 and beta-1,6 linkages. We have isolated the C. albicans cDNAs for KRE6 and SKN1, the genes required for beta-1,6-glucan synthesis in Saccharomyces cerevisiae. The results of Northern blot analysis revealed that C. albicans KRE6 was expressed at a higher level than SKN1 in the yeast phase, while SKN1 expression was strongly induced upon induction of hyphal formation. In addition, the C. albicans KRE6 and SKN1 mRNAs but not the actin mRNA were shortened during the yeast-hypha transition. Unlike S. cerevisiae, more than 50% of cell wall glucan was beta-1,6 linked in C. albicans. Neither beta-1,3-glucan nor beta-1,6-glucan was affected by the homozygous C. albicans skn1 delta null mutation. Although we never succeeded in generating the homozygous C. albicans kre6 delta null mutant, the hemizygous kre6 delta mutation decreased the KRE6 mRNA level by about 60% and also caused a more than 80% reduction of beta-1,6-glucan without affecting beta-1,3-glucan. The physiological function of KRE6 was further examined by studying gene regulation in C. albicans. When KRE6 transcription was suppressed by using the HEX1 promoter, C. albicans cells exhibited the partial defect in cell separation and increased susceptibility to Calcofluor White. These results demonstrate that KRE6 plays important roles in beta-1,6-glucan synthesis and budding in C. albicans.

Amino Acid Sequence↗

PubMed1997

Mutual inhibition by TGF-beta and IL-4 in cultured human bronchial epithelial cells.

The airway epithelial cell may play a role as an effector cell, releasing various cytokines and extracellular matrix components in immune responses, inflammation, and wound repair processes, thus contributing to cytokine "networks." The cytokines transforming growth factor (TGF)-beta and interleukin (IL)-4 are though to have pivotal roles in airway diseases, with IL-4 having proinflammatory actions and TGF-beta generally regarded to mediate repair and to attenuate immune responses. In asthma, where IL-4 and TGF-beta are thought to contribute to the inflammatory process and repair, respectively, interactions between these cytokines are likely to be of importance. Therefore, we studied the potential interaction of both cytokines by measuring IL-8 and fibronectin release by cultured human bronchial epithelial cells (HBECs). IL-4 is capable of inducing IL-8 release from HBECs. This effect of IL-4 can be blocked by the concurrent presence of the cytokine TGF-beta. In contrast, TGF-beta had a modest inconsistent stimulatory effect on IL-8 release by itself and had no effect on the IL-8 release induced by tumor necrosis factor (TNF)-alpha. An antagonistic effect of IL-4 and TGF-beta was also observed on HBEC fibronectin release. TGF-beta stimulated fibronectin release, and IL-4 was able to inhibit this. This effect was not due to a redistribution of fibronectin but appeared to be due to a true reduction in synthesis. Consistent with this, IL-4 and TGF-beta effects on IL-8 and fibronectin release were paralleled by changes in mRNA levels. The ability of TGF-beta to block IL-4-induced IL-8 release is certainly not the only mechanism to inhibit IL-8 release because dexamethasone was capable of inhibiting both TNF-alpha- and IL-4-induced release of IL-8. These results indicate that TGF-beta and IL-4 can have mutually inhibitory effects. The balance determined by this reciprocal inhibition may play an important role in regulating inflammation repair and in diseases such as asthma.

Adult↗

PubMed1997

Cigarette smoke induces interleukin-8 release from human bronchial epithelial cells.

Cigarette smoking causes the development of chronic bronchitis and chronic obstructive pulmonary disease. We hypothesized that exposure to cigarette smoke might initiate release of inflammatory mediators by bronchial epithelial cells. To evaluate this, the effect of cigarette smoke extract (CSE) on IL-8 release from cultured human bronchial epithelial cells was examined. CSE augmented IL-8 release from bronchial epithelial cells in a concentration- and time-dependent manner. Most of the augmenting activity of CSE on IL-8 release from bronchial epithelial cells was lost after volatilization or lyophilization treatment. Two major volatile factors in cigarette smoke, acrolein and acetaldehyde, augmented IL-8 release. Four cell strains were tested and showed increased IL-8 release in response to CSE. In addition, bronchoalveolar lavage was performed on 11 nonsmokers and 12 smokers. IL-8 concentration was greater in the proximal, bronchial samples than in distal, alveolar samples, and IL-8 in BAL from smokers was higher than in BAL from nonsmokers. There was a significant correlation between IL-8 concentration and neutrophil count in bronchial samples of BAL fluid. These data support the hypothesis that exposure to cigarette smoke may induce bronchial epithelial cells to release IL-8 and that this may contribute to airway inflammation in smokers.

Acetaldehyde↗

PubMed1997

Quantitative evaluation of the IL-1 beta and IL-1 receptor antagonist obtained from BALF macrophages in patients with interstitial lung diseases.

Our previous reports demonstrated the concomitant release of IL-1 beta and IL-1 inhibitory activity in the culture supernatants of BALF macrophages in both healthy subjects and patients with interstitial lung diseases. IL-1 inhibitory activities decreased in healthy smokers (HS), and patients with sarcoidosis (Sar), or idiopathic pulmonary fibrosis (IPF), compared with those in healthy nonsmokers (HNS), though an increase in IL-1 beta release was not detected. IL-1 inhibitory activity was mainly characterized as IL-1 receptor antagonist (IL-1ra). In this study, we confirmed a decrease in IL-1ra in terms of the amounts of protein (enzyme-linked immunoassay) and gene transcripts (reverse transcriptase polymerase chain reaction followed by high performance liquid chromatography). Imbalance between IL-1ra and IL-1 beta was expressed as a molar ratio of IL-1ra/IL-1 beta protein: (Sar; 4.20 +/- 2.06, IPF; 4.26 +/- 3.41, HS; 3.44 +/- 3.09 versus NS 8.33 +/- 2.77: P < 0.001). These results were similar in terms of the amounts of gene transcripts. In conclusion, the imbalance of IL-1 beta and IL-1ra production was confirmed at three levels: biological activity, amounts of protein, and gene transcript obtained from BALF macrophages in chronic inflammatory processes in the lungs.

Adult↗

PubMed1996

Lipid abnormalities of erythrocyte membranes in hemodialysis patients with chronic renal failure.

Lipids in erythrocyte membranes from 16 hemodialysis patients and 16 healthy volunteers were studied using gas chromatographic mass spectrometry. 7-keto cholestadiene was first reported in this study. The ratios of 7-keto cholestadiene to cholesterol, the ratios of arachidonate to cholesterol and the ratios of dochosahexanate to cholesterol in peak heights of chromatograms were measured in both groups as the markers of lipid peroxidation. Higher 7-keto cholestadiene/cholesterol ratios and lower arachidonate/cholesterol and dochosahexanate/cholesterol ratios were significantly observed in hemodialysis patients compared with healthy subjects. Our results are evidence that hemodialysis patients are exposed to much oxidative stress. It has been suggested that, during hemodialysis, leukocytes are activated by contract with non-physiological surfaces of the blood line tubing and produce oxygen free radicals. Oxygen free radicals attach cholesterol, arachidonate and dochosahexanate to produce lipid peroxides. In this study, this cell activation may be responsible for the increased lipid peroxidation of hemodialysis patients, 7-Keto cholestadiene, arachidonate and dochosahexanate can be used as markers of lipid peroxidation in hemodialysis patients.

Adult↗

PubMed1996

Lipopolysaccharide increases fibronectin production and release from cultured lung fibroblasts partially through proteolytic activity.

Fibronectin is a major product of fibroblasts and can mediate diverse functions including wound healing. Chronic bacterial infections are generally associated with a marked decreased in the ability to repair. We therefore hypothesized that bacterial endotoxin, lipopolysaccharide (LPS), might alter fibroblast fibronectin production. LPS augmented fibronectin production by fibroblasts and also stimulated the release of fibronectin from cell layers. An increase in new protein synthesis appeared to account for part of the increased fibronectin, because the inhibitor of protein synthesis, cycloheximide, inhibited the increase in total production of fibronectin. Cycloheximide did not attenuate the increased release of fibronectin into the culture medium. This increased release appeared to be caused, at least in part, by fragmentation of fibronectin by proteases contained in LPS preparations. In this regard all preparations of LPS tested were found to cleave fibronectin. Finally, zymograms indicated that LPS could also cleave gelatin with at least two bands of proteolytic activity but that it did not cleave bovine serum albumin or ovalbumin. These results indicate that the ability of bacterial products to alter fibronectin production and to degrade this macromolecule may account for altered wound repair that occurs with chronic bacterial infection.

Cell Line↗

PubMed1996

Role of three chitin synthase genes in the growth of Candida albicans.

The CHS2 and CHS3 genes of Candida albicans were disrupted. The double disruptant was still viable. Assessment of chitin and of calcofluor white resistance shows that CHS1 is responsible for septum formation and CHS3 is responsible for overall chitin synthesis otherwise. There were only small differences in virulence to immunocompromised mice of homozygous chs2 delta amd chs3 delta null mutants.

Animals↗

PubMed1996

Beta-adrenergic agonists attenuate fibroblast-mediated contraction of released collagen gels.

The effects of beta-adrenergic agonists on fibroblast-mediated collagen gel contraction were investigated. beta-Agonists isoproterenol and epinephrine significantly attenuated fibroblast-mediated gel contraction in a concentration-dependent manner, whereas alpha-agonist norepinephrine had no effect. The biologically active form of isoproterenol, (-)-isoproterenol, was 10-fold more effective than the optical isoform, (+)-isoproterenol. beta-Antagonists sotalol and propranolol reversed the attenuation caused by 10(-7) M isoproterenol or epinephrine at the concentration of 10(-7) M or 10(-6) M, but the alpha-antagonist phentolamine did not. However, beta1- or beta2-specificity of these effects is not clear. Isobutyl methylxanthine augmented the effect of isoproterenol and also prolonged the duration. Two reagents which are known to increase intracellular adenosine 3',5'-cyclic monophosphate (cAMP), prostaglandin E2 and dibutyryl adenosine 3',5'-cyclic monophosphate, attenuated gel contraction in a concentration-dependent manner. These data suggest that the fibroblast-mediated collagen gel contraction can be modulated by beta-adrenergic agonists and that the effect depends on cAMP.

1-Methyl-3-isobutylxanthine↗

PubMed1995

Characterization and gene cloning of 1,3-beta-D-glucan synthase from Saccharomyces cerevisiae.

1,3-beta-D-Glucan synthase of Saccharomyces cerevisiae was solubilized and purified up to 700-fold by product entrapment. The specific activity of the partially purified enzyme was around 4 mumol glucose incorporated.min-1.mg protein-1. In SDS/PAGE, enrichment of a 200-kDa protein was clearly observed in parallel with the increase in specific activity. mAbs that could immunoprecipitate the 1,3-beta-D-glucan synthase activity were isolated, and some of them also recognized this 200-kDa protein in the Western blot. Internal amino acid sequences of this 200-kDa protein were determined after lysyl endopeptidase digestion. With the information of these amino acid sequences, we cloned two genes, GSC1 and GSC2 (glucan synthase of S. cerevisiae 1 and 2), which are very similar to each other (88% at the amino acid level); hydropathy profiles of both proteins suggest that these genes encode integral membrane proteins which can be assumed to have approximately 16 transmembrane domains. Disruption of each gene was not lethal, but disruption of both genes was lethal. The 1,3-beta-D-glucan synthase activities of membrane and partially purified enzyme of gsc1::URA3 cells were significantly lower than those of the wild-type and gsc2::LEU2 cells.

Amino Acid Sequence↗

PubMed1995

Characterization of chitin synthase 2 of Saccharomyces cerevisiae. Implication of two highly conserved domains as possible catalytic sites.

Chitin synthase 2 of Saccharomyces cerevisiae was characterized by means of site-directed mutagenesis and subsequent expression of the mutant enzymes in yeast cells. Chitin synthase 2 shares a region whose sequence is highly conserved in all chitin synthases. Substitutions of conserved amino acids in this region with alanine (alanine scanning) identified two domains in which any conserved amino acid could not be replaced by alanine to retain enzyme activity. These two domains contained unique sequences, Glu561-Asp562-Arg563 and Gln601-Arg602-Arg603-Arg604-Trp605, that were conserved in all types of chitin synthases. Glu561 or arginine at 563, 602, and 603 could be substituted by glutamic acid and lysine, respectively, without significant loss of enzyme activity. However, even conservative substitutions of Asp562 with glutamic acid, Gln601 with asparagine, Arg604 with lysine, or Trp605 with tyrosine drastically decreased the activity, but did not affect apparent Km values for the substrate significantly. In addition to these amino acids, Asp441 was also found in all chitin synthase. The mutant harboring a glutamic acid substitution for Asp441 severely lost activity, but it showed a similar apparent Km value for the substrate. Amounts of the mutant enzymes in total membranes were more or less the same as found in the wild type. Furthermore, Asp441, Asp562, Gln601, Arg604, and Trp605 are completely conserved in other proteins possessing N-acetylglucosaminyltransferase activity such as NodC proteins of Rhizobium bacterias. These results suggest that Asp441, Asp562, Gln601, Arg604, and Trp605 are located in the active pocket and that they function as the catalytic residues of the enzyme.

Amino Acid Sequence↗

PubMed1995

Isolation of canCHS1A, a variant gene of Candida albicans chitin synthase.

A canCHS1A gene encoding the chitin synthase of Candida albicans was cloned. DNA sequencing and comparison with another canCHS1 gene described elsewhere indicated that the canCHS1A gene encoded a polypeptide with 775 amino acid residues, a protein with one less amino acid than that encoded by the canCHS1 gene. A six-base alteration was observed between the two genes, suggesting that the canCHS1A gene is a variant gene of the canCHS1. The pH profile/activity relationship of canChs1A in permeabilized cells was identical to that of canChs1. The canChs1A enzyme was competitively inhibited by polyoxin D (5.2 microM) and nikkomycin Z (12 microM). When the cloned gene was expressed in a Saccharomyces cerevisiae chs2 mutant that exhibited aberrant morphology, the normal structure was restored. We conclude that the function of the canCHS1A gene is similar to that of sacCHS2 in S. cerevisiae.

Aminoglycosides↗

PubMed1995

Bronchial epithelial cells regulate fibroblast proliferation.

Chronic bronchitis frequently leads to irreversible airway obstruction. Alteration of airway architecture with abnormal airway connective tissue is thought to play an important role in this process. We hypothesized that the epithelial cells that line the airways modulate the development of peribronchial fibrosis and fixed airway obstruction by directing fibroblast proliferation. To assess this, we examined stimulatory activities for human lung fibroblast proliferation in bovine bronchial epithelial cell-conditioned medium. The conditioned medium stimulated the proliferation of fibroblasts in a serum-free culture system in a concentration-dependent manner. The fibroblast growth stimulatory activity was heterogenous, with molecular masses of > 50 and approximately 10 kDa. Bronchial epithelial cell-conditioned medium also contained fibroblast growth inhibitory factors, including both transforming growth factor (TGF)-beta and, based on indomethacin sensitivity, cyclooxygenase products. TGF-beta appeared to contribute to the morphological change of fibroblasts induced by the conditioned medium. Co-culture of human lung fibroblasts with bronchial epithelial cells resulted in a stimulation of fibroblast proliferation. In summary, airway epithelial cells appear to regulate fibroblast proliferation and may play a role in peribronchial fibrosis in chronic bronchitis.

Animals↗

PubMed1995

Cigarette smoke inhibits lung fibroblast proliferation and chemotaxis.

Cigarette smoking is the most clearly recognized cause of pulmonary emphysema. Since loss of lung tissue, which characterizes emphysema, represents a balance between injury and repair, we hypothesized that cigarette smoke might contribute to the development of emphysema by inhibiting fibroblast proliferation and migration. To evaluate this, we examined the effect of cigarette smoke extract (CSE) on the proliferation and migration of human lung fibroblasts in vitro. CSE inhibited fibroblast proliferation and migration at noncytotoxic concentrations. When CSE was treated to remove volatile components, it showed less inhibitory activity on fibroblast proliferation. Therefore, we also examined acrolein and acetaldehyde, which are volatile components of cigarette smoke, Micromolar concentrations of acrolein and millimolar concentrations of acetaldehyde induced significant inhibition of fibroblast proliferation. In contrast, removal of volatile components did not eliminate the inhibitory activity of CSE for fibroblast migration, although acetaldehyde and acrolein alone were also capable of inhibiting chemotaxis. Cigarette smoke-induced inhibition of fibroblast proliferation and migration may impair lung repair following lung injury, and may thus contribute to the development of pulmonary emphysema.

Acetaldehyde↗

PubMed1995

Docosahexaenoic acid ethyl ester and its ultraviolet degradation products showed DNA-breaking activity in vitro and cytotoxic effects on the HSC-4 cell line.

The DNA-breaking activity and cytotoxicity of docosahexaenoic acid ethyl ester (DHAE) and its degradation products (dDHAE) induced by ultraviolet (UV) irradiation, were demonstrated in this study. The major component of dDHAE was identified as 4-hydroxyvaleric acid ethyl ester. DHAE and dHAE solutions at a concentration of 100 mg/ml induced single-strand breaks of plasmid DNA after an incubation at 37 degrees C and pH 7.6 for 15 hours. DHAE transformed a plasmid supercoiled DNA (Form I) into an open circular relaxed form (Form II), and dDHAE completely destroyed DNA molecules. HSC-4 cells, which were derived from human prickle cell carcinoma, were cultured with various concentrations (10, 30 and 50 micrograms/ml) of DHAE and dDHAE. Both inhibited the proliferation of HSC-4 cells. The potency of their cytotoxicity was dependent on their concentration. It is noteworthy that the lethal effects of DHAE and dDHAE on HSC-4 cells were quite similar, although the DNA-breaking activity of dDHAE was much greater than that of DHAE. These results suggested that DHAE becomes more cytotoxic after undergoing oxidization and metabolism in the cell.

Antineoplastic Agents↗