Sarcoma-180 Tumor Cells Research Articles

Poly-L-Lysine Inhibits Tumor Angiogenesis and Induces Apoptosis in Ehrlich Ascites Carcinoma and in Sarcoma S-180 Tumor

Background:This study focuses on the role of Poly-L-lysine (PLL), an essential amino acid, on molecular changes of tumor angiogenesis suppression, pro-apoptotic and anti-apoptotic gene expression after treatment on Ehrlich ascites carcinoma (EAC) and solid sarcoma-180 tumor cells bearing mice.Materials and Methods:The cell viability was carried out using MTT assay. The antitumor activity was evaluated by treatment with PLL at 20 and 40mg/kg/b.w doses for 14 days in EAC ascites tumor and 21 days for Sarcoma-180 solid tumor model. Several tumor evaluation studies, haematological and biochemical parameters were estimated. Importantly, the tumor cell apoptosis was assessed using microscopic observations, DNA fragmentation assay, Flow cytometric analysis, cell-cycle and electron-microscopic study, following which, the expression of several signal proteins related to pro-apoptosis, anti-apoptosis and tumor angiogenesis were quantified using western blotting and immunohistochemistry study.Results:Precisely, PLL had cytotoxic effect on K562; A549; U937 and B16F10 cancer cells. Significant decreases in liquid and solid tumors and increased life span of treated mice were observed (P<0.05). Typical morphological changes, apoptosis bleb phenomenon and sub-G1 cell cycle arrests revealed that PLL promoted apoptotic cell death. Western blot and immunohistochemistry confirms, PLL activated apoptotic signalling cascades through down regulation of Bcl-2 and CD31 protein and up-regulation of Bax and p53 proteins. The anti-angiogenic effects were also accompanied with decreased VEGF expression and reduced peritoneal-angiogenesis and microvessel density.Conclusions:The antitumor and antitumor-angiogenic activity of PLL was confirmed from all the results via up and down regulation of relevant signal proteins reported in this publication.

Replica exchange molecular dynamics simulations reveal the structural and molecular properties of levan-type fructo-oligosaccharides of various chain lengths

BackgroundLevan and levan-type fructo-oligosaccharides (LFOs) have various potential applications in pharmaceutical and food industries due to their beneficial properties such as their low intrinsic viscosity and high water solubility. Previous studies showed that they exhibited prebiotic effects, anti-inflammatory and anti-tumor activities against Sarcoma-180 tumor cells of human. Despite their various potential applications, the structural and molecular properties of LFOs of various chain lengths are not well understood.ResultsWe employed the replica-exchange molecular dynamics simulations method (REMD) in AMBER14 to elucidate structural and molecular properties of LFOs with chain lengths of 5 (LFO5), 10 (LFO10) and 15 (LFO15) residues in two models of generalized Born implicit solvent (GBHCT and GBOBC1). For LFO10 and LFO15, four distinct conformations (helix-like, partial helix, zig-zag and random structures) were characterized by their upper-middle and lower-middle torsions. For LFO5, two distinct conformations (partial helix and random structures) were characterized by their middle torsion and molecular angle of residues 1, 3 and 5. To determine hydrogen bonds important for the formation of helix-like structures of LFO10 and LFO15, occurrence frequencies of hydrogen bonds were analyzed, and the O6(i)--H3O(i+1) hydrogen bond was found with the highest frequency, suggesting its importance in helix formation. Among three dihedral angles between two fructosyl units [ϕ (O5’-C2’-O6-C6), ψ (C2’-O6-C6-C5) and ω (O6-C6-C5-C4)], dihedral angle distributions showed that ω was the most flexible dihedral angle and probably responsible for conformational differences of LFOs.ConclusionsOur study provides important insights into the structural and molecular properties of LFOs, which tend to form helical structures as the chain length increases from 5 to 15 residues. This information could be beneficial for the selection of LFOs with appropriate lengths and properties for pharmaceutical and biological applications.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1182-7) contains supplementary material, which is available to authorized users.

Cytoxicity and apoptotic mechanism of ruthenium(II) amino acid complexes in sarcoma-180 tumor cells.

Over the past several decades, much attention has been focused on ruthenium complexes in antitumor therapy. Ruthenium is a transition metal that possesses several advantages for rational antitumor drug design and biological applications. In the present study, five ruthenium complexes containing amino acids were studied in vitro to determine their biological activity against sarcoma-180 tumor cells. The cytotoxicity of the complexes was evaluated by an MTT assay, and their mechanism of action was investigated. The results demonstrated that the five complexes inhibited the growth of the S180 tumor cell line, with IC50 values ranging from 22.53 µM to 50.18 µM, and showed low cytotoxicity against normal L929 fibroblast cells. Flow cytometric analysis revealed that the [Ru(gly)(bipy)(dppb)]PF6 complex (2) inhibited the growth of the tumor cells by inducing apoptosis, as evidenced by an increased number of Annexin V-positive cells and G0/G1 phase cell cycle arrest. Further investigation showed that complex 2 caused a loss of mitochondrial membrane potential; activated caspases 3, caspase-8, and caspase-9 and caused a change in the mRNA expression levels of caspase 3, caspase-9 as well as the bax genes. The levels of the pro-apoptotic Bcl-2 family protein Bak were increased. Thus, we demonstrated that ruthenium amino acid complexes are promising drugs against S180 tumor cells, and we recommend further investigations of their role as chemotherapeutic agents for sarcomas.

영지(Ganoderma lucidum)의 β-Glucan에 의한 Sarcoma-180 육종암 생장 억제

버섯 다당류 <TEX>${\beta}$</TEX>-glucan의 항암 활성을 확인하기 위하여 영지균사체로부터 단백다당류(GLP)를 분리하고 Sarcoma-180 육종암을 이식시킨 마우스에 복강 투여하여 항암활성을 확인하였다. 육종암이 서혜부에 이식된 마우스에 GLP를 20 mg/kg의 농도로 10일간 복강투여 한 후 30일차에 확인한 결과, Sarcoma-180 육종암은 대조군대비 71.4% 억제되었으며, 마우스의 혈청, 종양조직 및 간조직 내의 TNF-<TEX>${\alpha}$</TEX>의 농도는 대조군보다 높게 나타났다. 따라서 GLP는 생체 내 TNF-<TEX>${\alpha}$</TEX>의 양적증가를 유도하며, 종양괴사 또는 에폽토시스와 연관된 육종암의 생장억제가 확인되었다. 이때 생장이 억제된 육종암 세포의 미세구조를 관찰한 결과, 상대적으로 큰 핵과 세포의 에폽토시스에서 전형적으로 보여지는 염색질 응축이 관찰되었으며, 핵막은 특징적으로 뭉쳐져 불규칙한 모양을 나타내었다. 따라서 영지에서 분리된 GLP는 종양 세포의 에폽토시스를 유도하여 종양의 성장을 억제하는 것으로 여겨진다. Mushroom-derived <TEX>${\beta}$</TEX>-glucan, a polysaccharide (GLP) isolated from the mycelium of Ganoderma lucidum, was previously shown to have inhibitory effects against tumor-bearing mice in vivo. We investigated the apoptotic effect of mushroom-derived <TEX>${\beta}$</TEX>-glucan in a sarcoma-180 tumor cell- bearing mice model using an ELISA to determine the levels of tumor necrosis factor-<TEX>${\alpha}$</TEX> (TNF-<TEX>${\alpha}$</TEX>) in the mice. The morphology of the tumor cells was assessed with transmission electron microscopy (TEM). GLP was injected into the tumor-bearing mice at a dose (i.p.) of 20 mg/kg for 10 days. After 30 days, the tumor mass from the inguinal region was collected, weighed, and assayed using TEM and a TNF-<TEX>${\alpha}$</TEX> ELISA kit. The tumors that developed in the mice treated with GLP were 71.4% smaller than those in the control group, showing the ability of GLP to inhibit tumor growth. The levels of TNF-<TEX>${\alpha}$</TEX> in the serum of the sarcoma-180 bearing mice were 12 times greater than in the serum of the nonbearing tumor mice. An ultrastructural study demonstrated that the GLP-treated sarcoma-180 tumor cells were condensed, with rearranged chromatin. In addition, the marginated chromatin in nucleus induced the nuclear compartment, and there were many vacuolization in the cell. GLP could be an effective apoptosis-inducing compound in sarcoma-type cancers.

Anti-tumour and immunomodulating activities of diosgenin, a naturally occurring steroidal saponin

Diosgenin is a naturally occurring steroidal saponin abundantly present in many medical plants. In this study, diosgenin could significantly inhibit the growth of sarcoma-180 tumour cells in vivo, and remarkably increase thymus and spleen weights of S-180-bearing mice and upgrade the secretion level of TNF-α in serum. Moreover, diosgenin could stimulate lymphocyte transformation and enhance phagocytic capability of macrophages in vitro, and remarkably promoted the secretion of NO and TNF-α in macrophages. These results suggested that diosgenin could improve both specific and non-specific cellular immune responses, and the anti-tumour effects of diosgenin were achieved by immunostimulating properties instead of direct cytotoxicity.

Antitumor efficacy and apoptotic activity of substituted chloroalkyl 1H-benz[de]isoquinoline-1,3-diones: a new class of potential antineoplastic agents

A series of ten chloroalkyl 1H-benz[de]isoquinoline-1,3-diones (naphthalimides) were synthesized and evaluated for antitumor activity. Amongst them, new compounds 2d and 2i carrying a 6-NO(2) substituent in the aromatic portion of the molecule possessed significant antineoplastic activity. The most active compound 2i had elicited significant cytotoxicity in 15 human tumor cell lines namely Leukemia: MOLT-4, HL-60; Lymphoma: U-937; Colon: 502713, HT-29, SW-620, HCT-15, COLO-205; Liver: Hep-2; Prostate DU-145, PC-3; Breast: MCF-7; Neuroblastoma: IMR-32, SK-N-SH and Ovary: OVCAR-5 out of the 17 cell lines screened. Flow cytometric analysis performed to study the effect of compound 2i on the progression of cell cycle of MOLT-4 cells, revealed rise in sub-G(1) fraction and concomitant accumulation of cells in S and G(2)/M phases, indicating apoptosis, mitotic arrest and/or delay in exit of daughter cells from mitotic cycle respectively. It also induced caspase-mediated apoptosis of MOLT-4 cells in a dose dependant manner. Light and electron microscopic studies revealed characteristic morphology of apoptotic MOLT-4 cells after in vitro treatment with 10 μM concentration of the compound. Apoptosis induction was also observed in HL-60 cells by compounds 2d and 2i to an extent much greater than camptothecin and cis-platin at 10 μM concentration. Both the compounds have shown minimal suppressive effect on human PBMC having high IC(50) values of 3,582 and 1,536 μM respectively. These compounds inhibited DNA and RNA synthesis in murine ascites Sarcoma-180 tumor cells in vitro at 8 μM concentration. Above results indicate promising chemotherapeutic potential of the key compound 2i.

Preparation and biological activities of chitosan from the larvae of housefly, Musca domestica

Many studies have indicated that the larvae of housefly possess excellent nutritional and pharmacological value. In the present study, the chitosan was isolated from the larvae of housefly, Musca domestica. Its antioxidant potencies were examined employing various established in vitro systems, such as 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, reducing power and metal ion chelating activity, and inhibitory effects against human cervical carcinoma (HeLa) and mouse sarcoma-180 (S-180) tumor cells were also tested. The results showed that the chitosan had stronger scavenging activity on DPPH radical than ascorbic acid. The half effective concentration on DPPH radical was approximately 0.373 mg/mL. The chitosan showed efficient reducing power and considerable ferrous ions chelating potency in this study. Moreover, chitosan from housefly larvae also exhibited significant antitumor activity against HeLa and S-180 tumor cell lines in vitro. The inhibitory effects of showed a dose-dependent manner and reached 50.8%, 52.9% at 1 mg/mL, respectively. These in vitro results suggested that the chitosan from the larvae of housefly could be effectively used as a natural antioxidant to protect the human body from free radicals and retard the progress of many chronic diseases. Furthermore, the chitosan with antitumor activity from the larvae of housefly might provide useful information for the development of antitumor drugs.

Anti-tumour and immuno-stimulating activities of the fruiting bodies of Paecilomyces japonica, a new type of Cordyceps spp.

The anti-tumor and immuno-stimulating activities of the fruiting bodies of Paecilomyces japonica (PJ), grown on silk-worm larvae and of Cordyceps sinensis (CS), a wild form of Cordyceps Fungi, were investigated. Ethanol extracts of both fungi, when administered for 9 consecutive days, at 50 and 100 mg/kg i.p., caused a significant increase in life span and a significant decrease in tumor weights and volumes, in mice inoculated with Sarcoma-180 tumor cells. Both fungal extracts were demonstrated to exhibit phagocytosis enhancing activity as measured by carbon clearance in mice. PJ extracts, when administered i.p. at 50 mg/kg/day for 3 consecutive days, exhibited a significant enhancement of phagocytosis, its potency as expressed by the regression coefficient ratio, RCtr/RCc, being 1.64 (the phagocytosis index = 2). This was approximately the same for that of zymosan (RCtr/RCc = 1.55, PI = 2), a typical phagocytosis enhancer, whereas CS extracts exhibited a moderate phagocytosis enhancing activity at the same dose level (RCtr/RCc = 1.30, PI = 1). Both fungal extracts caused a significant increase in an acid phosphatase activity, representing lysosomal enzymes, in macrophages at 20 and 100 micro g/ml in vitro, in compliance with in vivo results. These results suggest that the anti-tumor activity of both fungi might be related to an immuno-stimulating function.

The physicochemical properties and antitumor activity of cellulase-treated chitosan

Cellulase was used to partially hydrolyse N-acetylated chitosan. The hydrolysis process was monitored by gel permeation chromatography. Factors affecting the enzymatic hydrolysis of chitosan were studied. The degraded chitosans were characterized by X-ray diffraction, thermogravimetric analysis, differential thermal analysis, Fourier transform infrared and carbon-13 magnetic resonance spectra. The results showed that the enzymatic hydrolysis was by endo-action, and the total acetylation degree of chitosan did not change after degradation. The decrease of molecular weight led to transformation of crystal structure, alteration of thermostability and increase of water-solubility, but the chemical structures of residues were not modified. Most reducing end-residues of produced oligomers were GlcNAc units. This water-soluble product inhibited the growth of sarcoma180 tumor cells in mice with maximum inhibitory rates of 50% by intraperitoneal injection and 31% by oral administration.

Synthesis, Characterization and AntitumourActivity of Metal Complexes of 5‐Carboxy‐2‐Thiouracil

Metal complexes of 5-carboxy-2-thiouracil with Mn(ll), Co(ll), Ni(ll), Cu(ll), Zn(ll) and Cd(ll) ions were synthesized, characterized, and subjected to a screening system for evaluation of antitumour activity against Sarcoma-180 (S-180) tumour cells. The complexes were characterized by elemental analysis, infrared, electronic spectra, room temperature magnetic measurements and powder X-ray diffraction. The antitumour activity results indicate that some complexes have antitumour activity both in vivo and in vitro against S-180 tumour cells.

Cell Type and Spatial Location Dependence of Cytoplasmic Viscosity Measured by Time-Resolved Fluorescence Microscopy

Information on the cell type and spatial location dependence of cytoplasmic viscosity would be very useful in understanding some of the processes occuring in the cell. For this purpose, fluorescent dye kiton red (sulforhodamine B) was loaded into a variety of cells such as Swiss 3T3 fibroblasts, human mononuclear cells, Sarcoma-180 tumor cells, Chinese hamster ovary cells, plant cells fromDigitalis lanata,stamen hair cells ofTradescantia,and guard mother cells ofAllium cepa.Space-resolved measurements of cytoplasmic viscosity were carried out by using an experimental set-up wherein a picosecond laser system was coupled with an epifluorescence microscope. The spatial resolution of this set-up was ∼1.0 μm, and reliable dynamic fluorescence measurements could be obtained from 102to 103fluorescent molecules. Fluorescence lifetime measurements showed that a large fraction (∼70%) of kiton red was in the free form. Fluorescence anisotropy decay of kiton red in cells was analyzed by a two population (free and bound) model. The microviscosity of cytoplasm was estimated from the anisotropy decay kinetics of the free probe. It was found that the cytoplasmic viscosity is dependent on both the cell type and spatial location within a cell. Furthermore, both the average value of viscosity and spatial variation within a cell were larger in the plant cells when compared to the animal cells. Model studies in various simpler systems have shown that the higher viscosity observed in some part of the cell could be due to either physical restriction and/or the presence of high concentrations of small solutes and macromolecules.

Effects of Saffron on Vitamin A Levels and its Antitumour Activity on the Growth of Solid Tumours in Mice

AbstractInhibitory effects of saffron extract, a commonly used food spice, were studied against subcutane-ously inoculated solid Dalton's lymphoma ascites (DLA), Ehrlich ascites carcinoma (EAC) and Sarcoma-180 (S-180) tumours in mice. Oral administration of 100 mg/kg of the saffron extract significantly inhibited the growth of DLA and S-180 solid tumour by 87 and 41%, respectively. A dose of 150 mg/kg delayed the onset of tumour formation and inhibited further growth of a delayed Dalton's lymphoma ascites solid tumour by 80%. Chromium release cytotoxicity assay reflected the sensitivity of DLA and S-180 tumour cells to cytolysis (in vitro) in the presence of the extract. Estimation of serum vitamin A and β-carotene levels from S-180 tumour bearing mice treated with saffron extract indicated elevated serum levels of serum vitamin A and β-carotene. Chemical analysis of the antitumour compound from saffron extract indicated that crocin (a natural carotenoid) was responsible for the observed biological effect...

Effect of asoka on the intracellular glutathione levels and skin tumour promotion in mice

The bark of Saraka asoca (asoka) is commonly used to treat various diseases by the Indian system of medicine and in Sri Lanka. Further purification and chemical analysis of the active compound from the bark extract of asoka showed that (−)-epicatechin was responsible for the observed antitumour/anticarcinogenic activity. Papilloma formation in mice initiated with 7,12-dimethylbenz[ a]anthracene (DMBA) and promoted using croton oil was inhibted by the topical application of 100 mg/kg body weight (b.w.) of (−)-epicatechin isolated from asoka bark extract. Oral administration of the same dose restricted the growth of s.c. injected 20 methylcholanthrene (MCA) induced soil tissue fibrosarcomas significantly in mice. Elevations of almost 2–4-fold in the intracellular reduced glutathione and related enzymes viz., glutathione reductase and glutathione S-transferase of sarcoma-180 tumour cells were noted in the presence of 1 μg/ml of (−)-epicatechin, further highlighting its antiproliferative effect.

The Utility of Putrescine as a Splenic Immunofunctional Imaging Agent.

The spleen is the largest lymphoid organ. The uptake of 14C-putrescine in spleen increased 5 to 8 days after inoculation of sarcoma-180 tumor cells. This phenomenon is in accord with the increase of spleen weight, and its uptake by teatment with DFMO increased about 2 times that of nontreatment with DFMO. A correlation between the spleen weight and 14C-putrescine uptake in spleen is obtained. By i.p. administration of lentinan; immunopotentiator, the uptake of 14C-putrescine in spleen was significantly increased. Putrescine would be useful for a splenic immunofunctional imaging agent.

Fluoropyrimidine-mediated changes in small nuclear RNA.

Studies were completed to examine the effects of the antineoplastic agent 5-Fluorouridine (FUrd) on the metabolism of the small molecular weight nuclear RNA (snRNA). Cultured Sarcoma-180 murine tumor cells were exposed to FUrd concurrent with [3H]cytidine for 6 h, the drug was removed, and the RNA was isolated at 0, 24, or 48 h following the drug treatment. The results of these studies demonstrated that FUrd produced three dose-dependent changes in snRNA metabolism. The electrophoretic migration of the U4 and U6 snRNA was altered in nondenaturing 10% polyacrylamide slab gels. These results were not observed in denaturing gels or when RNA was extracted at temperatures exceeding 25 degrees C, suggesting that the incorporation of 5-fluorouracil induced secondary structural changes in these RNA. A dose- and time-dependent selective reduction in the turnover of the U1 snRNA synthesized in the presence of FUrd was observed as well, with levels over 100% higher than control cells at 48 h after exposure to 10 microM FUrd. These changes in snRNA metabolism may contribute to the reported alterations in large molecular weight RNA metabolism that also result in fluoropyrimidine-treated cells, or to cytotoxicity.

Immunological studies on sporamycin-treated animals.

Sporamycin showed a remarkable tumor regressive activity against sarcoma-180 with a single 5 mg/kg dose of intravenous administration. This antitumor effect on tumor and host animals was examined immunologically. As the results: (1) When sarcoma-180 tumor cells were used as an antigen macrophage migration inhibition reaction by spleen cells derived from the tumor-bearing mice treated with sporamycin was positive at day 7 approximately 14 after the medication and was negative thereafter. (2) The delayed hypersensitivity tested by the foot-pad reaction was positive in tumor-bearing mice treated with sporamycin, and no decrease of foot pad reaction was observed, whereas this reaction decreased remarkably in non-treated tumor-bearing mice. (3) Sarcoma-180 tumor cells were mixed with spleen cells derived from sporamycin-treated mice, and were inoculated into normal dd mice. The growth of tumor cells was inhibited markedly, but no inhibition of tumor growth was observed in case of spleen cells derived from non-treated tumor bearing mice. (4) Combined treatment of sporamycin with PS-K, an immunopotentiator, showed a remarkable synergistic effect.

Molecular changes in cell surface membranes resulting from trypsinization of sarcoma 180 tumor cells

Sarcoma-180 tumor cells in culture or grown as an ascites form in the CD-1 mouse have been subjected to mild trypsinization procedures in order to study morphological and molecular changes resulting from proteolysis. The cells attached to a substratum become rounded within 20 min and most undergo cell division, but they do not detach from the substratum. Removal of trypsin permits the cells to go back to their original spindle shape over an 8–20 h period. Surface membranes were isolated from trypsinized ascites and cultured cells and subjected to dodecyl sulfate-acrylamide gel electrophoresis. Both cell types showed the same two kinds of changes in electrophoretic patterns. First, there was a loss of glycoproteins from both cell types, even though they show different complements of cell surface glycoproteins. Second, there is a loss of high molecular weight polypeptides, which have previously been suggested to play a role in membrane stabilization and cell shape. These results further implicate these polypeptides in the control of cell morphology and offer circumstantial evidence for transmembrane interactions of surface glycoproteins with the high molecular weight polypeptides as a factor in controlling cell morphology.

Effect of antitumor agents on sarcoma-180 tumor cells transplanted to liver, kidney, and lung.

The survival time of animals, inhibition of the incorporation of thymidine-[6-3H] (3H-TdR) into DNA, and histopathological observation were made after the injection of Mitomycin-C, Bleomycin, cyclophosphamide, Daunomycin, Actinomycin-D, or 5-fluorouracil into mice transplanted with sarcoma-180 to their liver, kidney, and lung. The most prolonged survival time was obtained by the injection with cyclophosphamide and a moderate prolonged survival by Bleomycin and Actinomycin-D. In the case of 5-fluorouracil and Daunomycin, there were extreme variations in the survival time depending on the site of tumor growth. Cyclophosphamide and 5-fluorouracil showed greater and longer lasting inhibition of the incorporation of 3H-TdR into DNA of the tumor tissue, whereas the remaining agents caused transient inhibition on the tumor tissue. Inhibitory ratio and duration of the incorporation of 3H-TdR into DNA of normal site of the tissue of tumor-bearing organ were found to be more increased or almost the same compared with those of the tumor tissue. The most rapid recovery of the incorporation of 3H-TdR into DNA was observed in the small intestine among various organs and tumor in any treatment groups. From the histopathological observation, the degree of tumor cell damage by the agent was almost in agreement with inhibition of the incorporation of 3H-TdR up to 72 hr after the treatment.

Biological effects of anthramycin methyl ether. II. Inhibition of DNA synthesis in the intestinal epithelium and sarcoma-180 tumor cells.

The temporal course of DNA synthesis after subcutaneous injection on Anthramycin Methyl Ether (AME) was investigated in Sarcoma-180 ascites tumor cells and in the proliferative cells of the intestinal epithelium. Both cell types demonstrated dramatic inhibition of DNA synthesis: however, there was no appreciable difference in response of the 2 cell systems to the drug. After sub-lethal doses, recovery was seen to occur in an oscillatory fashion which eventually reached control values. This pattern of recovery suggested partial <i>in vivo </i>synchronization of the proliferative cell population, which could be due to preferential block in one stage of cell cycle or selective killing of cells in a sensitive stage.

Inhibition of DNA synthesis in sarcoma-180 tumor cells in vitro by dimethyl sulfoxide.

SummaryDMSO was found to inhibit DNA synthesis in S-180 ascites tumor cells in vitro. This inhibition was a linear function of DMSO concentration from 5 to 15% (v/v). Removal of the DMSO resulted in an immediate restoration of the capacity for TdR-3H incorporation.