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In the course of malignant growth processes in patients with lung cancer, a decrease of natural cytotoxic activity of peripheral blood lymphocytes was observed. This process was accompanied by changes of activities of two lysosomal enzymes, arylsulfatase and acid phosphatase, suggesting participation of these enzymes in manifestation of effector functions of lymphocytes in cancer patients. The level of activity of granular enzyme, beta-glucuronidase, remained unchanged at all stages of disease. A study of natural killer activity of C3HA mice splenocytes after inoculation of transplantable hepatoma 22-a cells revealed a relative stability of the level of their cytotoxicity, and of the activities of lysosomal enzymes--arylsulfatase, acid phosphatase, alpha-mannosidase, acid lipase, N-acetyl-beta-D-glucosidase, and beta-galactosidase, beginning from the 3rd day after hepatoma implantation.

Effects of two immunosuppressors, cyclophosphane abd 5-fluorouracyl, used in clinical practice for treatment of oncological diseases, were assessed in respect to cytotoxicity and activity of several lysosomal enzymes located in splenocyte granules of C3HA mice. 48 h after a single intraperitoneal injection, both preparations produced a marked decrease in their cytotoxic activity, which was accompanied by a pronounced splenopathy. Both preparations were shown to decrease activity of arylsulfatase. Administration of cyclophosphane brought about the rise of activity of acid lipase as compared to control. Activities of acid phosphatase, alpha-mannosidase, beta-galactosidase, and N-acetyl-beta-D-glucosidase did not change after administration of the used immunosuppressors. It may be suggested that only arylsulfatase and acid lipase are involved in performance and(or) manifestation of the natural killer activity in splenocytes of the C3HA mice after their administration with cyclophosphane or 5-fluorouracyl.

Effects of polyamine (PA) synthesis inhibitors--alpha-difluoromethylornithinchloride (DFMO) and alpha-methylornithinchloride (MO)--separately or in combination with the epidermal growth factor (EGF)--on lysosome-phagosome fusion (P-LF) and F-actin content in murine peritoneal macrophages were studied using fluorescent dye Acridine orange for lysosome labelling, FITC-phalloidin for F-actin, and yeast cells as a target. DFMO and MO significantly inhibited P-LF and decreased F-actin content in murine peritoneal macrophages. A combination of DFMO and MO with EGF failed to inhibit P-LF or to decrease F-actin content in these cells. The results obtained with DFMO and MO suggested new cellular targets of their effects. These results may be extended to cancer research to provide a rationale for clinical trials using combinations of EGF with DFMO or MO.

Effect of DNA-intercalators ethidium bromide (EB, 0.005 and 0.015 mM) and dimidium bromide (DB, 0.005 and 0.010 mM) and antioxidative compounds acetylsalicylic acid (ASA, 0.05 and 0.50 mM) and beta-carotene (0.01, 0.02, 0.05 mM) on the phagosome-lysosome (P-L) fusion and F-actin content in murine peritoneal macrophages were studied. EB, DB, ASA and beta-carotene were found to stimulate P-L fusion and the effect depending on the concentration of compounds tested. The strongest influence as evoked by 0.5 mM of ASA and 0.05 mM of beta-carotene. The compounds tested enhanced the F-actin content in macrophages, especially by the action of beta-carotene (0.05 mM). The obtained data indicate a correlation between P-L fusion stimulation and F-actin content under the influence of compounds tested in murine peritoneal macropheages.

Effects of biologically active compounds bilirubin (BR, 0.1 and 0.2 mM), chelerythrine (CR, 0.1 and 0.5 mM) and farmorubicin (FR, 0.6 and 6.0 mM) on the phagosome-lysosome fusion (P-LF) were studied using fluorescent dye acridine orange for lysosomal labelling and yeast cells as a target. To investigate mechanisms of these effects, changes in fluidity of lysosomal membranes from murine liver were studied by measuring of fluorescence intensity, lifetime and polarization of the fluorescent membrane probes: DPH (1,6-diphenyl-1,3,5-hexatriene) and TMA-DPH [1-(4-triphenylamino)-6-phenyl-1,3,5-hexatriene] incorporated in isolated murine liver lysosomes. In order to characterize the induced cytoskeleton changes, the F-actin content in murine peritoneal macrophages was determined. It was found that all three compounds tested enhanced P-LF. Our results demonstrate that BR induces a decrease in DPH and TMA-DPH fluorescence polarization, FR increases DPH and TMA-DPH fluorescence polarization, and CR causes an increase in TMA-DPH fluorescence polarization in lysosomal membranes. All the three compounds increase F-actin content in peritoneal macrophages. Thus, the action of BR extended on P-LF is associated with increasing lysosomal membranes fluidity and cytoskeleton changes. The enhancement of P-LF under the action of FR and CR can be most likely explained by changes of cytoskeleton.

Current literature on the structure of vacuolar apparatus and its involvement in the process of intracellular transport has been reviewed. Modern views on endocytosis and its particular steps are described. Special attention is paid to one of important steps of endocytosis-the phagosome-lysosome fusion, its disturbance under the action of pathogenic microorganisms, its inhibition and stimulation by some chemical factors and biologically active compounds. The authors widely used their own experimental data. Much attention is paid to the current notions on the fusion pore structure and function, as well as on fusion mechanisms of biological membranes and factors regulating this process.

It is known that spermidine and other naturally occurring polyamines accumulate in rat lung slices by an energy-dependent uptake process and that alveolar macrophages (AM) have a greater rate of uptake than has the total lung cell population. In the present study rat AMs were incubated with spermidine, which resulted in a marked and significant (P < 0.002) decrease in phagocytosis of heat-killed yeast cells at concentrations 0.2 and 0.5 mM and a tendency to decrease at 0.05 mM. The number of microtubules surrounding the centrioles was measured using electron microscopy and appeared to be decreased at concentrations 0.2 and 0.5 mM. There was no affect on phagolysosomal pH. The results suggest that spermidine might affect the defense against inhaled pollutants and microbes, especially when spermidine levels are increased, as they are under conditions with high mitotic activity, e.g., in tumors.

It has been shown by electrophoresis that the earlier obtained thermoresistant sublines of the CHO-K1 cell line do not accumulate heat shock proteins when cultured at 37 degrees C. The thermostability of two lysosomal proteins--acid lipase and acid phosphatase--were higher in the thermoresistant cells than in the parental cells, whereas no differences in thermostability of galactosidase were found between heat resistant and parental lines. Thus, it is concluded that changes in the level of conformational flexibility of protein molecules may be one of the mechanisms of cell adaptation to growth at higher temperatures.

Effects of various antituberculosis remedies (ATR)--isoniazid (INA), saluzid (SA), streptosaluzid (SS), ethambutol (EB), sodium para-aminosalicylate (SPAS) on phagosome-lysosome (PL) fusion, on F-actin content in mouse macrophages and on G-actin polymerization in vitro were studied. The ATR of choice have been shown to stimulate the PL fusion. INA (0.2 mM), SA (0.02 mM), SS (0.05 mM), EB (0.08 mM) and SPAS (0.5 mM) increased the F-actin content and changed its localization within macrophages. ATR changed the character of G-actin polymerization in vitro. Possible mechanisms of interrelation between cytoskeleton (actin part) changes and PL fusion are discussed. The results obtained suggest to use the ATR-induced changes in PL fusion and F-actin content in the cells for estimating therapeutic effects of respective antituberculosis remedies.

It has been shown that during novocaine (4.6 x 10(-3) M) induced formation of the segregation apparatus (SA) the total protein synthesis decreases, the synthesis of certain proteins being characterized by a high rate turnover. In the intact erythrocytes, 1 x 10(-2) cycloheximide (CHM) inhibits the novocaine induced formation of segregation apparatus (SA) and protein synthesis by 90%. The combined action of novocaine and CHM on erythrocytes is accompanied by a decrease in CHM inhibiting effect on protein synthesis. This effect retains for 1.5 h during the action of both compounds. Some vacuoles of SA disposed cytochemically exposed acid phosphatase (AP), which enabled us to consider these as lysosomes. According to AP distribution in lysosomes, they can be classified into 3 groups. In group 1 AP is distributed along the membrane of vacuoles, in group 2 it is associated with the material inside the lysosome, and in group 3 the enzyme is both distributed along the membrane and associated with the material enclosed within the segregation vacuole. Such a mode of AP distribution reflects presumably the functional heterogeneity of lysosomes.

The influence of natural and synthetic polyamines, phalloidin, cytochalasin D, vinblastine, colchicine, puromycin, chlorpromazine, urea, glutaraldehyde, and ethanol on the phagosome-lysosome fusion and the content of F-actin in murine peritoneal macrophages has been studied. Fluorescent phallotoxin FITC-phalloidin was used to stain F-actin. Natural polyamines (spermine, spermidine, putrescine), phalloidin, ethanol (0.1 M) stimulated the phagosome-lysosome fusion and increased the mid-content of F-actin in macrophages. Cytochalasin D, vinblastine, colchicine, puromycin, chlorpromazine, urea, glutaraldehyde, ethanol (0.15 and 0.2 M) inhibited this process and decreased the mid-content of F-actin. Possible mechanisms of the interconnection of cytoskeleton and the phagosome-lysosome fusion are discussed.

The paper deals with the examination of the role of phagocytes--alveolar macrophages and neutrophils--and peripheral monocytes, in the pathogenesis of idiopathic fibrosing alveolitis (IFA). As the disease aggravates, activation of the absorbing capacity of monocyte-macrophagal cells corresponds to a sharp rise in the level of circulating immune complexes in the blood of IFA patients. Higher activities of elastase and collagenase are observed in the IFA patients' bronchial lavage fluid.

Diamines (DA), characterized by a general formula H2N-(CH2) n-NH2 in which n varies from 2 to 10, inhibit the phagosome-lysosome fusion in murine peritoneal macrophages. The DA concentration was 0.2, 0.5 and 1.0 mM. The inhibitory effect increased with increasing the number of CH2-groups in the DA molecule. It was suggested that DA could influence the lysosomal membrane state. An additional proof of such changes was obtained with 1,6-diphenyl-1,3,5-hexatrien (DPH) as a fluorescent probe. Lysosomes isolated from murine peritoneal macrophages by differential centrifugation were used. It was found that DPH fluorescence intensity in lysosomal membrane increased under the influence of DA.

The natural killer activity (NKA) of human mononuclear cells and the activity of the lysosomal enzymes of these cells (arylsulfatase, acid phosphatase and beta-glucuronidase) has been studied in norm and under human lung cancer. The mononuclear cells were isolated from peripheral blood of 10 healthy donors and 20 patients with lung cancer of II-III stages. Under the action of mononuclear cells on the target cells (human erythroleukosis cells K-562 labeled with 3H-uridine) the NKA of mononuclear cells of patients was seen to decrease (cytotoxic index = 54.8 +/- 6.4%), in comparison with that of healthy donors (cytotoxic index = 65.1 +/- 4.5%). Simultaneously a decrease in arylsulfatase activity (0.05 +/- 0.01 nmoles/10(6) cells/min) was found in comparison with the control value (0.11 +/- 0.01 nmoles/10(6) cells/min). In 2-3 weeks after the operation the NKA value (cytotoxic index = 50.2 +/- 5.8%) was restored and arylsulfatase activity (0.09 +/- 0.02 nmoles/10(6) cells/min) was increased. There was no correlation between the NKA value and the activities of acid phosphatase and beta-glucuronidase. The parallelism observed between changes in NKA value and arylsulfatase activity may suggest a possible participation of this enzyme in the killing mechanism at the stage of cerebroside sulfate ester degradation of the target cell membrane to initiate the lytic events.

Polyanion (mannansulphate), cation dyes (Toluidine blue, Nile blue), anion-dye (Trypan blue) also non-electrolytes (urea, glutaraldehyde) were found to inhibit the phagosome-lysosome fusion in murine macrophages. The mechanism of this effect is discussed.

Kinetics of sanguiritrine consumption by L cells of LSM substrain was studied in cell culture. About half of the drug used was absorbed by cells within 20 min. Sanguiritrine inhibited the lysosomal hydrolases (cathepsin D, beta-D-galactosidase and N-acetyl-beta-D-glucosaminidase) activity by 50% at concentration 2.10(-4) M. The drug a concentration 4.10(-4) M inhibited acid lipase by 55% and acid phosphatase by 58%.

The enantiomeric and diastereoisomeric analysis of nonproteinogenic methyl and hydroxy amino acids, obtained by asymmetric synthesis with the aid of a chiral regenerable reagent, has been carried out by liquid chromatography.

The influence of polyamines on the phagosome-lysosome fusion in murine peritoneal macrophages and on polymerization of G-actin from the rabbit muscle in vitro has been studied. Both natural polyamines (spermin, spermidin, putrescin) and synthetic phenyl derivates of polyamines (3,3'-diaminobensidin, 1,5-naphtalin diamine, 4,4'-diaminodiphenilmetan, dancylcadaverin) were used. Unlike the phenyl derivates of polyamines and putrescin, spermin and spermidin stimulate the phagosome-lysosome fusion to induce G-actin polymerization. Possible mechanisms of action of the above polyamines are discussed.

The incubation of frog erythrocytes in the Ringer solution with novocaine (4.6 x 10(-3) M) during 24 hours at 10 degrees C provoked vacuole formation (segregation zones). Changes of the novocaine solution for a fresh Ringer solution and the following 48 hour incubation was accompanied by a decrease in the number of vacuoles both electron-translucent and containing membranous material. Simultaneously, the number of vacuoles with amorphous material only and with amorphous and membranous substances was seen to increase. Under the action of cycloheximide (1.10(-2) M) or oligomycin (2.5 x 10(-6) M) on erythrocytes with preformed vacuoles for 48 hours the total number of vacuoles and their dimensions decreased, with numerous amorphous inclusions appearing. Vacuoles with amorphous and membranous material increased in size. Similar ultrastructural changes in the segregation zones under the influence of both the inhibitors were observed showing the appearance of thick threads and a decreased share of electron-translucent vacuoles. A specific effect of cycloheximide, compared to that of oligomycin, involved the expansion of smooth endoplasmic reticulum cisternae. Under the influence of novocaine, 3H-leucin incorporation in proteins of frog erythrocytes was intensified. However, this incorporation was considerably inhibited by cycloheximide. Erythrocytes with segregation zones were more inhibitor susceptible than erythrocytes without vacuoles. The inhibitory effect was stronger early after their administration to the incubation medium, compared to the later periods.

Novocaine segregation zones in frog's erythrocytes, isolated by differential centrifugation, were shown to be ATPase active. The enzyme displays half of its maximum activity at 0.18 Mm ATP concentration to be inhibited by high concentrations of ATP. ATPase is activated by both Mg2+ and Ca2+ (in a lesser degree), with the maximum activity being at pH 7.5. A 5 minutes heating without the substrate results in decreasing the enzyme activity at 30 degrees, and in the total inhibition at 50 degrees C. Along with ATP, the enzyme can hydrolyse GTP and, in a lesser degree, ADP and sodium pyrophosphate. The ATPase activity is not effected with oligomycin (0.5-1.5 mkg/ml) or ouabaine (0.1 mM). Oligomycin in concentration 5 micrograms/ml induced non-specific inhibition of ATPase. Uncouplers, like 2,4-dinitrophenol and carbonyl cyanid p-trifluorometoxyphenylhydrazone, stimulate the enzyme activity. The lack in the ATP-ase sensitivity to oligomycin (specific inhibitor of mitochondrial F1-ATPase) and ouabaine (specific inhibitor of Na+, K+-ATPase) may suggest that the ATPase activity of novocaine segregation zones in frog's erythrocytes is not associated with a random contamination with mitochondria or cytoplasmic membranes. The ATPase under study has much in common with the lysosomal +H-ATPase. The results obtained support a hypothesis that +H-ATPase may function as a course of protones for maintaining acidic medium in segregation zones and promote accumulation of weak bases by means of their protonation.

Granules arising in the cytoplasm of Rana temporaria erythrocytes incubated in either solution containing acridine orange, chloroquine or antibiotic daunorubicine were studied cytophotometrically. The stuff concentrations in the granules were estimated under various conditions of incubation. The stuff concentrations in the granules appeared to be 1000-fold higher than in the incubation solutions. The average concentration in the granules did not depend on either the initial concentration of the stuff solution or the incubation time. The stuff concentration in the granules decreases with the increase of the granule size. Mechanisms of cation-acid segregation and accumulation by living cell are discussed.

Activities of lysosomal enzymes (acid phosphatase, N-acetyl-beta-D-glucosaminidase, acid lipase and cathepsin D) have been examined in a synchronized culture of mouse L-fibroblasts. Cell synchronization was achieved by the double thymidine block with a subsequent mitotic selection after colcemid treatment. Specific activities of the enzymes studied were found to be higher in S-G2 that in G1. There is a linear increase (approximate doubling) in enzyme activities per cell from G1 to M. Activity of galactosyltransferase, a marker of the Golgi apparatus, declined in mitotic cells in comparison with the interphase cells. Ultrastructural examination of L-cells revealed a reduction of the intracellular membrane system including the Golgi apparatus during mitosis. Changes in the Golgi apparatus activity have been considered as a possible regulatory point of lysosome formation. The data presented are compared with the results of morphological studies of lysosomal system in L-cells.

No lysosomes were found in the frog intact erythrocytes with electron microscope. Under the influence of neutral red (NR-8.7.10(-5) M) and novocaine (N-4.6.10(-3) M) segregation zones (vacuoles) including these substances are formed. Using electron microscopy and morphometry the action of NR and N for 5 minutes up to 48 hours was found to provoke the formation of four types of vacuoles differing in their morphology: with electron-transparent content, with amorphous inclusions and membrane whorls. The dynamics of vacuole formation, of their changes and amount were followed depending on the time of exposition of these substances. Biochemical investigation of both NR and N isolated vacuoles showed in these some activities of lysosomal marker enzymes--acid phosphatase and N-acetyl-beta,D-glucosaminidase. Ultrastructural investigation of acid phosphatase localization in the isolated vacuoles revealed the histochemical reaction product mainly in electron-translucent vacuoles (primary lysosomes) and partly in electron dense ones (secondary lysosomes). On the ground of the above studies a conclusion is made that in frog erythrocytes treated with NR and N lysosome formation is induced to be followed by the induced autophagocytosis and heterophagocytosis. Some possible ways of the vacuolar system formation in frog erythrocytes and the origin of lysosomal hydrolases are discussed.

Using supravital fluorescent staining of lysosomes with Euchrysine 3R, the morphology of these organelles was studied in L cells examined from cultures being at different growth phases in the course of cell cycle and after adipocyte conversion of L cells due to the 60% bovine serum administration. As cells were passing from the lag-phase to the stationary phase of culture growth, the number of lysosomes was seen to increase. The appearance of large lysosomes is characteristic of cells in confluent and senescent cultures. During G1-period, lysosomes are often confined to the perinuclear area of L-cells, to be extended later during S and G2-periods. In dividing cells, these are commonly seen scattered throughout the cell periphery, around the mitotic spindle. In cells undergoing differentiation, within 4-7 days the seeding in the medium supplemented with 60% bovine serum, the number of lysosomes became augmented to be gradually reduced during the next 10-15 days, concomittantly with the accumulation of lipid drops in the cell cytoplasm. The activity of the Golgi complex and the intensity of autophagy are discussed as possible regulation points of lysosome formation during the cell growth.

Effects of inhibitors of energy metabolism and protein synthesis on Neutral red segregation in frog erythrocytes were studied. Inhibitors of both glycolysis and respiration significantly reduced formation of segregation zones. This influence was most striking with antimycin A, rotenone and cyanide. This indicates that intact respiratory pathways may play an important part in the process of Neutral red segregation. Such uncouplers as FCCP (carbonyl cyanide p-trifluoromethoxyphenylhydrazone) and 2,4-dinitrophenol (DNP) as well as inhibitors of oxidative phosphorylation (arsenate and azide) are also very effective in inhibiting the Neutral red segregation at low concentrations. The effects of these uncouplers and of olygomycin suggest an important role of ATP as an energy source for the segregation process. An inhibitor of protein synthesis, such as cycloheximide, produces some reduction in segregation zones formation. Trapping of Neutral red by protonation could readily explain the high level of this dye accumulation in nucleated erythrocytes. The fact that low concentrations of FCCP and DNP inhibit the process of segregation brings a supporting evidence for the possibility of the ATP-driven proton pump involved in Neutral red segregation.

Numerous granules are formed in frog erythrocytes under the influence of cardiotrast (C) (diethanolamine-3,5-diiodo-4-pyridone-1-acetic acid). However, as revealed by cytospectrophotometric investigation and X-ray microanalysis, no C was accumulated in these granules. It is known that C can dissociate into diethanolamine and 3,5-diiodo-4-pyridone-1-acetic acid. It was assumed that under the influence of C granule formation may occur at the expense of an uncharged diethanolamine form penetrating into lysosome-like structures to be accumulated by protonation process. Diethanolamine was found to provoke granule formation in frog erythrocytes. It is impossible to reveal substance in granules because it is colourless and has no ultraviolet absorbtion band. Under the influence of some inhibitors of energy metabolism on granule formation and the granules formed, their inhibitory effect is exerted on the process of granule formation. In granules isolated by differential centrifugation activity of some marker lysosomal enzymes was found which enabled us to attribute these granules to lysosome-like structures.

Effects of some metabolic inhibitors, as well as of biologically active compounds (diakarb, ethidium bromide and a phenanthridine alkaloid sanguinarine) on the formed novocaine and neutral red segregation zones were studied. The volume of granules diminished under the influence of a glycolytic inhibitor iodoacetate, uncouplers of oxidative phosphorylation (2,4-dinitrophenol and carbonyl cyanide trifluoromethoxyphenylhydrozone), and respiratory inhibitors (antimycin A and rotenone), as well as under the influence of cycloheximide - an inhibitor of protein synthesis. Diakarb, ethidium bromide or sanguinarine also provoked a regression of the segregation zones. It has been found that all these compounds are inhibitors of ATPase activity of the isolated segregation zones. A possible mechanism of volume decreasing in segregation zones under the influence of both the metabolic inhibitors and diakarb, ethidium bromide and sanguinarine is discussed.

Anoxia (during 2 minutes after decapitation) produced a significant elevation of cAMP contents (up to 410%) in mouse brain cells. This effect was abolished by an intraperitoneal injection of alloxan (A), morphine (M), and ethanol (E) 30 minutes before decapitation, and after a 2 minutes diethyl ether (DE) inhalation. It was found that anoxia produced some decrease in phosphodiesterase (FDE) activity. A preliminary injection of A and E produced an activation of FDE; M and DE did not change FDE significantly. Mechanisms of action of all the four agents on the cAMP content under anoxia are different. A and E produced a rapid cAMP hydrolysis on stimulating the activity of FDE, M and DE inhibited apparently adenylate cyclase. The activation of adenylate cyclase due to anoxia is considered as one of the initial steps in the cell injury extention.

Kinetics of Neutral red (NR) and Acridine orange (AO) uptake by cultured L cells (subline LSM) has been studied. It was found that the uptake of both NR and AO, with their constant concentrations in the medium was characterized as a two-phase process. During 2 hours, these cells concentrated as much as 90% of the total amount of NR and AO taken up during the whole incubation period. The segregation and accumulation of NR, AO as well as NH4Cl took place in lysosomes. NR and AO concentrations within the cells exceed by 600 and 400 times, respectively, those in the medium. NR, AO and NH4+ accumulation in cells resulted in inhibition of the activity of the following lysosomal hydrolases: cathepsins B and D, acid lipase, N-acetyl-beta,D-glucosaminidase, beta-galactosidase, acid phosphatase and galactosyltransferase, the latter being a marker of Golgi apparatus. The effect of lysosomal enzyme activity inhibition on the cell economy, and a possible role of lysosomotropic agents as regulators of the lysosomal apparatus functional activity are discussed.

Current literature on the cell segregation function is reviewed. The modern data on the role of coated pits, coated vesicles and endosomes in receptor-mediated and fluid endocytosis are regarded. Mechanisms of segregation both of inorganic and organic substances in lysosomes are considered. A special attention is paid to the selective accumulation in lysosomes of substances penetrating through plasma membrane. Some modern considerations concerning the role of the ATP-dependent proton pump in maintaining low intralysosomal pH and accumulation of weak bases in lysosomes by means of protonation are given. A great attention is paid to the effect of accumulated foreign substances in lysosomes on lysosomal apparatus functions and some metabolic disorders as consequences of it. The importance of the cell segregation functions and of lysosomotropic compounds for cytopharmacology and cytopathology is emphasized.

Activities of lysosomal enzymes acid phosphatase, N-acetyl-beta-D-glucosaminidase, beta-galactosidase, acid lipase and cathepsins B and D were studied after accumulation of neutral red, acridine orange chloroquine and daunorubicin in lysosomes of fibroblasts of the LSM substrain. All the drugs studied proved to be inhibitors of these enzymes except of daunorubicin, which stimulated acid lipase activity. Lysosomotropic drugs are considered as possible regulators of the activity of lysosomes.

CAMP in the wide range of concentrations (3.10(-7)--10(-3) M), cGMP (10(-6)--10(-5) M) and dibutyril-cAMP (3.10(-6) M) produced no effect on oxidative phosphorylation of rat liver mitochondria. Among histone fractions (H1, H3 and H4) tested, the arginine-rich fraction H3 (18 microgram/mg of mitochondrial protein) produced a strong uncoupling effect. It is supposed that the effect of cAMP on oxidative phosphorylation of mitochondria may be carried out indirectly through activation of protein kinase, phosphorylation of histones, and their release into the cytoplasm.

Kinetics of chloroquine and daunorubicin (DNR) uptake by cultured L cells (subline LSM) has been studied. With their constant concentrations in the medium the uptake of both chloroquine and DNR was characterized as a two phase process. Within 1.5-2 hours, these cells accumulated as much as 90 per cent of the total chloroquine and DNR amounts taken up during the whole incubation period. The segregation and accumulation of these substances took place in lysosomes. Chloroquine and DNR concentrations within lysosomes exceed those in the medium by 1100 and 5000 times, respectively. The chloroquine and DNR accumulation in lysosomes inhibited activities of some lysosomal hydrolases tested: cathepsins B and D, N-acetyl-beta, D-glucosaminidase and acid phosphatase. Unlike, the activity of acid lipase was not affected by chloroquine, and was sufficiently stimulated (by 55%) by DNR. The mechanism of inhibition of lysosomal enzymes by chloroquine and DNR is not yet known, although some suggestions are made. Possible consequences of lysosomal activity inhibition for cell metabolism are discussed in addition to a possible role of lysosomotropic agents as regulators of lysosomal functional activity.