Combined effect of epinephrine and chalone extracted from Ehrlich ascites carcinoma administered during different time of day on cell division in the tumor

The biphasic circadian rhythm of mitotic activity has been demonstrated in a 5-day Ehrlich's ascites carcinoma (EAC) in mice. Adrenaline injected intraperitoneally in a dose of 1.5 micrograms/g bw produced an inhibitory effect on cell division that lasted over 4 hours and reached maximum at injection to mice during light time of the day. EAC extract in a dose of 1 ml also inhibited the mitosis during 4 hours, but the greatest fall in the mitotic activity was observed during the minimum mitotic activity in the control animals. Combined administration of adrenaline and the extract resulted in the phenomenon of prolonged inhibition of cell division, that persisted for maximum 6-8 hours, if the preparations were injected in the middle of the day light time. Of definite importance was the rhythm of changes in the sensitivity of proliferating tumor cells.     

Effect of a chalone-containing preparation from Ehrlich ascites tumor on DNA synthesis and cell division in the tumor in relation to the time of day

The mitosis inhibitory action of chalone-containing preparation of the Ehrlich ascite tumour was shown to depend on the time of its administration on round the clock, and on the circadian rhythm phase of the mitotic activity in this tumour. This allowed a conclusion that the chalone system of the tumour may be involved in the formation of the circadian rhythm of cell division. It was found that Ehrlich's ascite tumour chalone system regulated DNA synthesis influencing the cell passage from G1-phase of the mitotic cycle to S-phase, and the processes occurring during S-phase.     

An anticomplementary agent, K-76 monocarboxylic acid: its site and mechanism of inhibition of the complement activation cascade.

A monocarboxylic acid derivative (K-76 COOH) of K-76, purified from the culture filtrate of Stachybotrys complement I nov. sp. K-76, inhibits complement (C) activity. Its inhibitory action is mainly on C5 step. It strongly inhibits the generation of EAC1,4b,2a,3b,5b from C5 and EAC1,4b,2a,3b, and accelerates the decay of EAC1,4b,2a,3b,5b. It also causes some inhibition of the reactions of the reactions of C2,C3,C6,C7 and C9 with their respective preceding intermediate cells. It has no effect on the generation of EAC1,4b from C4 and EAC1, or of EAC-8 from C8 and EAC-7, and apparently increases the generation of EAC1,4b from C1 and EAC4b probably by inhibiting transfer or turnover of C1. It does not affect the rate of decay of EAC1,4b,2a or the T max of generation of EAC1,4b,2a, and it inhibits immune adherence only at high concentration. K-76 COOH also strongly inhibits hemolysis through the alternative pathway of C activation by cobra venom factor, but it does not seem to inhibit the early steps of the alternative pathway, because it has little affect on the consumption of C3 or the conversion of beta 1C to beta 1A on treatment of C serum with zymosan. K-76 COOH probably combines with C5 molecules, forming the inactive complexes, or it causes the structural alteration of C5.     

Absence of induction of IL-1 production in human monocytes by complement fragments

The ability of C fragments to induce IL-1 production in human monocytes was examined by using various approaches to carefully exclude the role of contaminating endotoxin. The presence of IL-1 activity in monocyte supernatants and lysates was assayed by the augmentation of PHA-induced proliferation of murine thymocytes. SRBC were opsonized with IgM rabbit antibodies and various human C components to prepare EAC reagents that contained less than 25 pg LPS/ml of EAC at 5 x 10(8) cells/ml. EAC1q, EAC4b, EAC4b2aoxy, EAC4b2aoxy C3b, EAC4b2aoxyC3bi, and EAC4b2aoxyC3d all failed to induce IL-1 production when incubated at 10- to 100-fold excess with adherent human monocytes. Similarly, LPS-free purified C3a, C5a, and C5a des Arg all showed no IL-1-inducing activities at concentrations up to 25 micrograms/ml. However, the same C5a preparations were active on human monocytes in the induction of chemotaxis, and C3a and C5a both induced skin-blueing in guinea pigs. Fragment Ba and Bb preparations purified by gel filtration chromatography contained approximately 100 pg LPS/micrograms Ba or Bb. These Ba and Bb preparations at 10 and 50 micrograms/ml, respectively, induced IL-1 production in the presence of 5 micrograms/ml polymyxin B (PMB). However, Ba and Bb preparations purified by affinity chromatography and HPLC contained lower levels of endotoxin contamination and displayed IL-1-inducing activities at Ba and Bb concentrations of 50 and 100 micrograms/ml, respectively, that were almost completely inhibited by PMB. To explore further the role of contaminating endotoxin, a Bb preparation was adsorbed with PMB-4B in the presence of a dialyzable detergent to remove LPS bound to the Bb. This LPS-free Bb preparation failed to induce IL-1 production while maintaining intact enzymatic activities. These results indicate that various solid phase or soluble C fragments, including C3b, iC3b, C3d, C3a, C5a, Ba or Bb do not induce IL-1 production in human monocytes in the absence of contaminating endotoxin.     

Effect of adrenaline on the mitosis-inhibiting action of a chalone-containing preparation in Ehrlich ascites tumor

The effect of adrenaline and Ehrlich ascite carcinoma (EAC) chalone on cell division was studied. It has been established that EAC chalone inhibited cell proliferation. The action of adrenaline was also accompanied by a decrease in mitotic index, but the inhibitory effect of the hormone was weaker than that of chalone, it occurred later and its duration was less. A combined effect of adrenaline and chalone depended on the time interval between the administration of the substances. It has been found that chalone administration 1 h after adrenaline administration prolonged mitotic inhibitory effect by 4 h and its synchronous action on cell division in EAC was weak during the experiment. Combined effect of adrenaline and chalone did not differ from the effect of chalone alone if chalone was administered 3 h after adrenaline administration.     

The modifications of the final stages of the complement reaction by alkali metal cations.

We studied the effects of alkali metal cations on the terminal stages of complement lysis of human and sheep HK erythrocytes. Sensitized erythrocytes (EA) were reacted with limited amounts of complement for 1 hr at 37 degrees C in buffer containing 147 mM NaCl (Na buffer), which resulted in 10-40% lysis. The unlysed cells were washed with Na buffer at 0-2 degrees C and incubated for 1 hr at 37 degrees C in buffers containing 147 mM of the various alkali metal cations. Although additional lysis (25 to 65%) occurred with K, Rb, or Cs buffer, only minor degrees developed with Na or Li buffer, only minor degrees developed with Na or Li buffer. Intermediate levels occurred with 100 mM of the divalent alkali cations. Halogen ions and SCN-(147 MM), Ca++ (0.15mM), and Mg++ (0.5 mM) did not alter the effect of the alkali metal cations. Lysis occurring in K+, Rb+ or Cs+ proceeded without lag, was temperature dependent with an optimum of 43 degrees C, and had a pH optimum of 6.5. Lysis in K and Na buffers was unaffected by 10(-3) to 10(-5) M ouabain. Experiments with mixtures of cations indicated that Na+ had a mild inhibitory effect that could be totally overcome by K+, partially by Rb+, and not at all by Cs+. Li+ had a strong inhibitory effect, 6 X 10(-5) M causing 50% inhibition in buffers containing 147 mM K+, Rb+, or Cs+. By using intermediate complexes of EA and purified complement components we demonstrated that K+ enhances the lytic action of C8 on EAC1-7 as well as that of C9 on EAC1-8. It was known that Li+ facilitates lysis when acting on the entire complement reaction. We found that Li+ enhanced the lytic action of C8 on EAC1-7, with a kinetic that differed from that of the K+ effect. In addition, Li+ inhibited the enhancing effect of K+ upon lysis of EAC1-8 by C9. This occurred at concentration of Li+ similar to those which inhibited the additional lysis by K+, Rb+, and Cs+ of cells that were pretreated in Na buffer with the entire complement sequence. We propose that the major effects of alkali metal cations on complement lysis are due to their interaction with C8 and/or membrane constitutes.     

Studies on the terminal stages of immune hemolysis. IV. Effect of metal salts.

The inhibitory effect of metal salts on the formation and transformation of E to ghosts was studied. Ferrous and ferric salts inhibited the binding of C9 to EAC1-8 cells but had no other inhibitory role in the reaction. Uranly, copper, and zinc salts inhibited the transformation of the EAC1-9inserted intermediate to E ghosts. This inhibition occurred at a stage prior to detectable damage as measured by 86Rb or hemoglobin release and at a step prior to that inhibitable by high molarity EDTA. Consequently a further step in the reaction sequence of E to ghosts was identified. The reaction sequence leading from EAC1-9 to ghosts can be summarized as follows: formula: (see text).     

Sex attractants for six clearwing and tineid species (Lepidoptera, Sesiidae and Tineidae) from Kazakhstan and Lithuania

Sex attractants for 3 Sesiidae and 3 Tineidae moth species in West-Kazakhstan and Lithuania were discovered by field screening tests of (3Z,13Z)-, (3E,13Z)- and (2E,13Z)-octadecadien-1-ols and their acetates as well as of some binary mixtures of these compounds. Total amount of chemicals was 0.3 mg/dispenser. Males of Synanthedon serica were attracted by a 5:5 mixture of 3E,13Z-18:OAc and 2E,13Z-18:OAc, Chamaesphecia bibioniformis by a 9:1 mixture of 3Z,13Z-18:OAc and 3E,13Z-18:OAc, Paranthrene tabaniformis by a 1:9 mixture of 3Z,13Z-18:OH and 3E,13Z-18:OH, Tinea nonimella by a 1:9 mixture of 3E,13Z-18:OH and 2E,13Z-18:OH, Monopis monachella by a 1:9 mixture of 3Z,13Z-18:OH and 2E,13Z-18:OH, and Nemaxera betulinella by a 9:1 mixture of 2E,13Z-18:OAc and the corresponding alcohol. The periods of attraction to the traps were registered for males of S. serica and Ch. bibioniformis and were found to occur at 15-18 and 15-17 o'clock, local time, respectively.     

Inhibition of type 1 and type 2 5alpha-reductase activity by free fatty acids,active ingredients of Permixon

In different cell systems, the lipido-sterolic extract of Serenoa repens (LSESr, Permixon inhibits both type 1 and type 2 5alpha-reductase activity (5alphaR1 and 5alphaR2). LSESr is mainly constituted of fatty acids (90+/-5%) essentially as free fatty acids (80%). Among these free fatty acids, the main components are oleic and lauric acids which represent 65% and linoleic and myristic acids 15%.To evaluate the inhibitory effect of the different components of LSESr on 5alphaR1 or 5alphaR2 activity, the corresponding type 1 and type 2 human genes have been cloned and expressed in the baculovirus-directed insect cell expression system Sf9. The cells were incubated at pH 5.5 (5alphaR2) and pH 7.4 (5alphaR1) with 1 or 3nM testosterone in presence or absence of various concentrations of LSESr or of its different components. Dihydrotestosterone formation was measured with an automatic system combining HPLC and an on-line radiodetector.The inhibition of 5alphaR1 and 5alphaR2 activity was only observed with free fatty acids: esterified fatty acids, alcohols as well as sterols assayed were inactive. A specificity of the fatty acids in 5alphaR1 or 5alphaR2 inhibition has been found. Long unsaturated chains (oleic and linolenic) were active (IC(50)=4+/-2 and 13+/-3 microg/ml, respectively) on 5alphaR1 but to a much lesser extent (IC(50)>100 and 35+/-21 microg/ml, respectively) on 5alphaR2. Palmitic and stearic acids were inactive on the two isoforms. Lauric acid was active on 5alphaR1 (IC(50)=17+/-3 microg/ml) and 5alphaR2 (IC(50)=19+/-9 microg/ml). The inhibitory activity of myristic acid was evaluated on 5alphaR2 only and found active on this isoform (IC(50)=4+/-2 microg/ml).The dual inhibitory activity of LSESr on 5alpha-reductase type 1 and type 2 can be attributed to its high content in free fatty acids.     

Anti-tumor promoting diterpenes from the stem bark of Thuja standishii (Cupressaceae).

Three new labdane-type diterpenoids, labda-8(17),13-dien-15,12R-olid-19-oic acid (1), 12S-hydroxylabda-8(17),13(16),14-trien-19-oic acid (2) and 13-ethoxylabda-8(17),11,14-trien-19-oic acid (3), along with known diterpenoids, trans-communic acid (4), totarol (5), 12-methoxyabieta-8,11,13-trien-11-ol (6), and 7 alpha,8 alpha-epoxy-6 alpha-hydroxyabieta-9(11),13-dien-12-one (7) were isolated from the stem bark of Thuja standishii. The structures of 1--3 were established by spectroscopic methods and chemical conversion. These compounds together with standishinal (8), 12-hydroxy-6,7-seco-abieta-8,11,13-trien-6,7-dial (9) and 6 alpha-hydroxysugiol (10) were tested for their inhibitory effects on Epstein--Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), as a test for potential cancer chemopreventive agents. Compound 10 showed strong inhibitory effect on EBV-EA induction (100% inhibition at 1000 mol ratio/TPA), and compounds 2 and 6 showed moderate inhibitory effects on EBV-EA induction. In addition, 15-oxolabda-8(17),11Z,13E-trien-19-oic acid (11) was found to exhibit the anti-tumor promoting activity in two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene and TPA.     

Synthesis and structure–activity relationships of 2- and/or 4-halogenated 13β- and 13α-estrone derivatives as enzyme inhibitors of estrogen biosynthesis

Ring A halogenated 13α-, 13β-, and 17-deoxy-13α-estrone derivatives were synthesised with N-halosuccinimides as electrophile triggers. Substitutions occurred at positions C-2 and/or C-4. The potential inhibitory action of the halogenated estrones on human aromatase, steroid sulfatase, or 17β-hydroxysteroid dehydrogenase 1 activity was investigated via in vitro radiosubstrate incubation. Potent submicromolar or low micromolar inhibitors were identified with occasional dual or multiple inhibitory properties. Valuable structure–activity relationships were established from the comparison of the inhibitory data obtained. Kinetic experiments performed with selected compounds revealed competitive reversible inhibition mechanisms against 17β-hydroxysteroid dehydrogenase 1 and competitive irreversible manner in the inhibition of the steroid sulfatase enzyme.     

Chromosomes 17 and 22 involved in marker formation in neurofibrosarcoma in von Recklinghausen disease

Summary We describe the cytogenetic findings in a recurrent neurofibrosarcoma in a patient with nonfamilial von Recklinghausen disease. The composite karyotype was: 40,Y,-X,+dic r(X;20)(:Xp22.2q26::20p13 q13:), -1, +der(1)t(1;3) (p21;p24),-3,-4,-5,+der(5) t(5;?)(q31;?),-9,-9,+der(9)t(3;9)(q21 or q13;p24 or p22), -11,+der(11)t(11;?)(q22.2;?), -17,+der(17)t(17; 22;?)(q21;q13.1;?), -20, -21, -22, -22, +der(22)t(17; 22;?)(q21;q13.1;?),t(2;10)(q37;q22). The derivative chromosomes were demonstrated at the 500 band level. Chromosomes 17 and 22 were shown to be involved in an unbalanced three-way translocation: t(17;22;?)(q21;q13.1;?). This event was confirmed by in situ hybridization, using two probes mapped to chromosome 17. Hill H is a probe derived from the novel oncogene TRE and is located at 17q12–22. The second probe, derived from the granulocyte colony-stimulating factor (G-CSF), is located at 17q11–q21. The rearrangement between chromosomes 17 and 22 showed breakpoints similar or close to the gene loci for neurofibromatosis 1 (NF-1) and NF-2. Based on our observations we recommend that genetic studies on NF-1 tumors include both gene sites (NF-1 and NF-2) rather than focus on one gene locus.     

A combined genetic and physical map of the Streptomyces coelicolor A3(2) chromosome.

The restriction enzymes AseI (ATTAAT), DraI (TTTAAA), and SspI (AATATT) cut the Streptomyces coelicolor A3(2) chromosome into 17, 8, and 25 fragments separable by pulsed-field gel electrophoresis (PFGE). The sums of their lengths indicated that the chromosome consists of about 8 Mb of DNA, some 75% more than that of Escherichia coli K-12. A physical map of the chromosome was constructed for AseI and DraI, using single and double digests, linking clones, cross-hybridization of restriction fragments, and locations of genetically mapped genes, insertion sequences, prophages, and the integrated SCP1 and SLP1 plasmids on the physical map. The physical map was aligned with the previously established genetic map, revealing that the two long opposite quadrants of the genetic map that are almost devoid of markers (the silent regions at 3 o'clock and 9 o'clock) are indeed physically long rather than being hot spots for genetic exchange. They must therefore contain long stretches of DNA different in function from the remainder of the genome. Consistent with this conclusion are the locations of significant deletions in both of the silent regions. Of these, a 40-kb deletion in the 9 o'clock region accompanied or followed integration of the SCP1 linear plasmid to produce the NF fertility state. PFGE analysis of Streptomyces lividans 66, a close relative of S. coelicolor A3(2), was hampered by the previously described susceptibility of its DNA to degradation during electrophoresis. However, ZX7, a mutant derivative of S. lividans lacking the DNA modification responsible for this degradation, yielded good PFGE preparations. Not more than 7 of the 17 S. coelicolor AseI fragments could be shared by the S. lividans strain.     

Discovery of novel histone lysine methyltransferase G9a/GLP (EHMT2/1) inhibitors: Design,synthesis, and structure-activity relationships of 2,4-diamino-6-methylpyrimidines

The discovery and optimization of a novel series of G9a/GLP (EHMT2/1) inhibitors are described. Starting from known G9a/GLP inhibitor 5, efforts to explore the structure-activity relationship and optimize drug properties led to a novel compound 13, the side chain of which was converted to tetrahydroazepine. Compound 13 showed increased G9a/GLP inhibitory activity compared with compound 5. In addition, compound 13 exhibited improved human ether-a-go-go related gene (hERG) inhibitory activity over compound 5 and also improved pharmacokinetic profile in mice (oral bioavailability: 17 to 40%). Finally, the co-crystal structure of G9a in complex with compound 13 provides the basis for the further development of tetrahydroazepine-based G9a/GLP inhibitors.     

On the mechanism of cell membrane damage by complement: evidence on insertion of polypeptide chains from C8 and C9 into the lipid bilayer of erythrocytes

The preceding paper (Hammer, C.H., A. Nicholson, and M. M. Mayer, 1975, Proc. Natl. Acad. Sci., 72:5076) presented evidence on insertion of polypeptide chains from the C5b and C7 subunits of C5b, 6, 7 complex into the phospholipid bilayer of erythrocyte membranes. In the present study, EAC1-8 and EAC1-9 (sheep erythrocytes carrying rabbit antibody and complement proteins C1 through C8 or C9, respectively), prepared with either 125I-C8 or 125I-C9, were incubated with trypsin or chymotrypsin and the release of 125I was measured. Only 9 to 19% of the specifically bound radioactivity was released. In addition, elution experiments were performed with 0.02 M EDTA-1.0 M NaCl. This solution did not elute C9 from EAC1-9. By contrast cellbound C9 was recovered from erythrocyte membranes with sodium dodecyl sulfate (SDS). Thus, enzymatic stripping and elution experiments indicate that cellbound C9 behaves like an integral membrane protein, presumably due to insertion into the lipid bilayer. EAC1-9 membranes that had been subjected to extended digestion with trypsin or chymotrypsin were extracted with SDS to recover the enzyme-resistant part of the C9 molecule from the membrane. Even though this domain of C9 carried 90% of the radioiodine associated with native C9, its m.w. was found to be only 18,000 daltons by analysis on SDS-PAGE. This represents one-quarter of the native C9 molecule.     

Muraymycins,novel peptidoglycan biosynthesis inhibitors: semisynthesis and SAR of their derivatives

Sixteen muraymycin derivatives 2-17 were synthesized based on selective reactions of the primary and secondary amino groups of muraymycin C1 (1) with isocyanates and aldehydes. Disubstituted derivatives 3-9 demonstrated no activity against either MraY or MurG at 相似文献   

(10E,12Z,15Z)-9-hydroxy-10,12,15-octadecatrienoic acid methyl ester as an anti-inflammatory compound from Ehretia dicksonii

The methanol extract of Ehretia dicksonii provided (10E, 12Z, 15Z)-9-hydroxy-10,12,15-octadecatrienoic acid methyl ester (1) which was isolated as an anti-inflammatory compound. Compound 1 suppressed 12-Otetradecanoyl-phorbol-13-acetate (TPA)-induced inflammation on mouse ears at a dose of 500 microg (the inhibitory effect (IE) was 43%). Linolenic acid methyl ester did not inhibit this inflammation at the same dose. However, the related compounds of 1, (9Z,11E)-13hydroxy-9,11-octadecadienoic acid (5) and (9Z,llE)13-oxo-9,11-octadecadienoic acid (6), showed potent activity (IE500 microg of 63% and 79%, respectively). Compounds 1, 4 ((9Z, 12Z, 14E)-16-hydroxy-9,12,14-octadecatrienoic acid), 5 and 6 also showed inhibitory activity toward soybean lipoxygenase at a concentration of 10 microg/ml.     

The developmental study on the third coronary artery of human being

The 3rd coronary artery, whose anatomical significance is defined, is a normal variant of the conus branch of the right coronary artery. This study involved the stereoscopic comparative investigation of human fetal hearts from 13 to 40 weeks of age and human adult hearts from 18 to 88 a of age. The incidence of the 3rd coronary artery in human fetuses was 45 out of 218 or 20.6%. No clear sexual differences were observed. Anastomoses had already developed between the 3rd coronary and the branches of the left anterior descending artery during the fetal stage. The 3rd coronary artery orifices in human fetuses was located at 9 o'clock (+/- 0 degree) most frequent (48.9%), and at 8 o'clock (-30 degrees) most infrequent (22.2%). The incidence of the 3rd coronary artery in human adults was 36.8%. In the human adult's normal group, the orifice was located at 9 o'clock (+/- 0 degree) most frequent (59.0%), and at 8 o'clock (-30 degrees) most infrequent (14.8%), while on the other hand in the pathologic group, the orifice was located at 9 o'clock (+/- 0 degree) most frequent (54.9%) and at 10 o'clock (+30 degrees) most infrequent (11.5%). Further, multiple 3rd coronary artery orifices, which were not observed in human fetal hearts, were observed in the human adults' heart. Furthermore, the existence of multiple orifices and the fact that human adult hearts had a higher incidence than human fetal hearts suggests the possibility that the 3rd coronary artery develops after birth.     

Some characteristics of human adrenal microsomal 21-hydroxylase activity

The following general characteristics of 21-hydroxylase activity were determined using pooled microsomes obtained from three glands. Enzyme activity exhibited a broad pH dependence, being optimal between pH 7.4-pH 7.8, and was maximal with NADPH in the range 2 to 4.75 X 10(-4)mol/l. No microsomal 21-hydroxylase activity was detected in the absence of NADPH or substrate and when heat denatured microsomes were employed. Enzyme activity was depressed by greater than 75% in the presence of 100% oxygen or nitrogen. In a second set of experiments, microsomal fractions were prepared individually from 7 glands. In the presence of 17 alpha-hydroxy progesterone (2.0 X 10(-7) and 2.0 X 10(-6)mol/l) product formation was linear with time for up to 90 s when the microsomal protein concentration was 5, 10 and 20 micrograms/ml. Between 5 and 30% of the substrate was converted during the first 60 s. In 5/7 of the glands the addition of the autologous cytosol (20 micrograms protein/ml) was without effect, and enzyme activity (using a 60 s reaction and either 2.0 X 10(-7) or 2 X 10(-6)mol/l 17 alpha-hydroxy progesterone was directly proportional to the microsomal protein concentration (range 0-20 micrograms/ml). With the other 2 adrenals 21-hydroxylation was not proportional to the same range of microsomal protein concentrations, although it became so upon the addition of cytosol, which significantly augmented activity. There was considerable variation in enzyme activity between glands from different individuals (Vmax ranging from 2.6 to 16.6 X 10(-9) mol/min/mg protein) and in the apparent Km's (from 0.22 to 1.1 X 10(-6)mol/l). In the two preparations sensitive to cytosol, the Vmax increased 2-fold, and the Km was 3 times lower. Cytosol was without effect upon the kinetic characteristics of the other 5 microsomal preparations. Ascorbic acid (1 X 10(-3) mol/l) depressed enzyme activity by 25-43% whereas oxidised and reduced glutathione (1 X 10(-3) mol/l) showed a slight and variable effect upon 21-hydroxylation.     

Effect of different fractions obtained by gel filtration of a chalone-containing preparation from Ehrlich ascites tumor on mitotic activity and DNA synthesis in this tumor

The effect of various fractions of chalone-containing preparation from ascite Ehrlich's tumour obtained by gel filtration on ultragel Ac-A-44 on mitotic activity and DNA synthesis in the tumour has been studied. The chalone-containing preparation (alcohol precipitate) was shown to suppress entering of tumour cells into M- and S-phase and DNA synthesis. After gel filtration, the partial division of active chalone component which inhibits entering of cells into M- and S-phase took place. The component inhibiting DNA synthesis eluted with G1-chalone.