mercaptopurine and Carcinoma--Ehrlich-Tumor

Topics: Animals; Anti-Bacterial Agents; Antineoplastic Agents; Azaguanine; Azaserine; Carcinoma, Ehrlich Tumor; DNA; DNA, Neoplasm; Floxuridine; Fluorouracil; Folic Acid; Glutamine; Leukemia L1210; Mercaptopurine; Methotrexate; Mitomycin; Neoplasms; Neoplasms, Experimental; Pharmacology; Purines; Puromycin; Pyrimidines; Research; RNA; RNA, Neoplasm; Thioguanine; Thiouracil

The main purpose of the present investigation was to study the effect of cloturin on aerobic glycolysis, endogenous and exogenous respiration and the level of ATP in both Ehrlich ascites carcinoma (EAC) and P388 murine leukaemia cells incubated in vitro. Also its effect on the level of total (T-SH) and non-protein (NP-SH) thiol groups was investigated. A significant inhibition of aerobic glycolysis was found only in P388 cells after 60 min of cloturin action. Cloturin inhibited both endogenous and exogenous respiration of EAC with succinate as substrate. Cloturin decreased the level of ATP after 2 h incubation in both types of tumour cell. The level of NP-SH was decreased more than that of T-SH in both types of cell.

Topics: Adenosine Triphosphate; Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Energy Metabolism; Glucose; Glycolysis; Leukemia P388; Mercaptopurine; Mice; Mustard Compounds; Oxygen Consumption; Sulfhydryl Compounds; Tumor Cells, Cultured

N-(o-methoxyphenyl)-maleimide (I), an intermediate obtained during the synthesis of pyrrolidinedione-N-mustards, did not exhibit antitumor activity against Ehrlich (ascites) carcinoma. The effect of co-administration of (I), with established anticancer drugs was studied against P388 leukemia, S180 (ascites) and Ehrlich (ascites) carcinoma. A significant potentiation in the activity of 5-Fluorouracil (5-FU) against Ehrlich (ascites) carcinoma by (I) was observed. The possible mechanisms responsible for potentiation of the activity of 5-FU are presented.

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Ehrlich Tumor; Cyclophosphamide; Cytarabine; Fluorouracil; Maleimides; Mechlorethamine; Mercaptopurine; Mice; Mitomycin; Mitomycins; Vinblastine

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Cell Line, Tumor; Cell Survival; Cytarabine; Leukemia P388; Mercaptopurine; Mice; Mustard Compounds

The effect of cloturin on biosynthesis of DNA, RNA and proteins in both P388 and Ehrlich ascites carcinoma (EAC) cells have been studied in vitro. Biosynthesis of macromolecules indicated by the incorporation rate of [14C]adenine (DNA, RNA), [14C]thymidine (DNA), [14C]uridine (RNA) and [14C]valine (proteins) were studied for concentration (75 to 600 mumol/l) and time dependence. Cloturin inhibits incorporation of all 14C-precursors into the TCA-insoluble fraction of both types of cells in proportion to its concentration. The complete inhibition of 14C-precursors was reached at the highest concentrations of cloturin (300 and 600 mumol/l). The fact that incorporation of four precursors is inhibited suggests that the effect of cloturin lies at an underlying level of energy generation or transfer, rather than at specific reactions in the biosynthesis of DNA and proteins. The rate of DNA synthesis is rapidly affected by the lowering of the level of any of the four deoxyribonucleotide triphosphates. Interference with the generation of high-energy phosphate bonds is one of the mechanisms available for induction of nucleotide deficiency. A depletion of nucleotide pools can serve as an efficient tool to inhibit cellular growth and to induce cell death under some circumstances.

Topics: Adenine; Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; DNA, Neoplasm; Kinetics; Leukemia P388; Mercaptopurine; Mice; Mustard Compounds; Neoplasm Proteins; Neoplasms, Experimental; RNA, Neoplasm; Thymidine; Tumor Cells, Cultured; Uridine

The effects of cytostatic treatment on urinary polyamine excretion have been investigated in tumor-bearing (either Ehrlich carcinoma of S 180 sarcoma) and in tumor-free mice. The animals were exposed to single or multiple treatment with various doses of cyclophosphamide, 5-fluorouracil, or 6-mercaptopurine. Treatment invariably enhanced polyamine excretion dependent on dose and effectiveness of the cytostatic drug. The most pronounced increases were observed in the excretion of spermine and putrescine, with peak excretion usually occurring after 1-2 and 3-4 days, respectively. The urinary excretion of spermidine was relatively modest in untreated mice, but the increases observed following drug treatment were high in proportion. Significant differences in urinary polyamine excretion were observed between tumor-free and tumor-bearing animals following treatment with all cytostatic agents. Peak values were invariably higher in tumor-bearing mice even in those with small, barely detectable tumors. After discontinuation of treatment polyamine excretion returned to normal values and stabilized in groups in which regression predominated, whereas in those groups of animals which showed little or no tumor regression urinary polyamine levels gradually increased again during a 2-week observation period.

Topics: Animals; Carcinoma, Ehrlich Tumor; Creatinine; Cyclophosphamide; Female; Fluorouracil; Mercaptopurine; Mice; Neoplasm Transplantation; Polyamines; Sarcoma 180; Time Factors

A series of novel aziridinyl-substituted 1(2)H-indazole-4,7-diones and related 1(2)H-indazole-4,7-diones was synthesized and tested against Ehrlich ascites carcinoma growth in male CF1 mice. Ten of the test compounds, including two aziridinyl-substituted 1(2)H-indazole-4,7-diones, were found to be significantly active (inhibition of tumor growth greater than 80%) in the Ehrlich ascites carcinoma screen. Several structure-activity relationships were indicated for antitumor activity in this screen. An aziridinyl-substituted derivative, 5-aziridinyl-6-chloro-1H-indazole-4,7-dione (8a), also exhibited significant activity against the growth of P-388 lymphocytic leukemia cells in male BDF1 mice (% T/C = 145; % T/C greater than 125 is considered significant).

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Cell Division; Indazoles; Leukemia P388; Male; Mice; Pyrazoles

A series of novel substituted thiochromones and thiochroman-4-ones was synthesized. Compounds were designed as analogues of naphthoquinone and as potential "bioreductive alkylating agents" and were tested for antitumor activity. The lead compound, 3-(chloromethyl)thiochromone 1,1-dioxide (4), inhibited Ehrlich ascites tumor growth by 100% in CF1 male mice at 10 (mg/kg)/day ip. Similarly, 18 of the 29 related compounds demonstrated good activity in this tumor screen. Few definitive structure-activity correlations were evident regarding the nature of the 3-substituent. However, the 2,3 double bond and a sulfone or sulfoxide were required for activity. Four of the compounds synthesized showed marginal but significant activity against P-388 lymphocytic leukemia.

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Chemical Phenomena; Chemistry; Cyclic S-Oxides; Leukemia P388; Male; Mice

Effects of butoctamide (N-(2-ethylhexyl)-3-hydroxybutyramide, L-2) on the antitumor activity of 6-mercaptopurine (6-MP) against Ehrlich solid tumors in mice were investigated. No change was observed in tumor growth after either oral or intraperitoneal administration of butoctamide (100 mg/kg/day X 7). This drug increased the activity of a low dose of 6-MP (2.5 approximately 10 mg/kg/day. i.p., X 7), but did not change the activity of a high dose of 6-MP (40 approximately 80 mg/kg/day, i.p., X 7). The antitumor activity of thioinosine (6-MP riboside) was similarly increased by administration of butoctamide (100 mg/kg/day, i.p., X 7). On the other hand, concomitant administration of butoctamide with cyclophosphamide, methotrexate, mitomycin C or adriamycin had no effect on the activity of these anticancer drugs. In butoctamide (100 mg/kg/day, i.p., X 7)-treated mice, the antitumor activities of a single administration of 6-MP and cyclophosphamide were not increased. Butoctamide stimulated the hypoxanthine-guanine phosphoribosyltransferase activity and inhibited the xanthine oxidase activity of mouse liver, to a certain degree as compared to controls. Butoctamide may promote conversion from 6 MP to thioinosinic acid monophosphate to a biologically active state, rather than to thiouric acid or hypoxanthine which would be inactive.

Topics: Amides; Animals; Carcinoma, Ehrlich Tumor; Hydroxybutyrates; Hypoxanthine Phosphoribosyltransferase; Liver; Male; Mercaptopurine; Mice; Thioinosine; Xanthine Oxidase

Diazomethyl ketone and chloromethyl ketone analogues prepared from N-tosyl amino acids have been synthesized and tested for antitumor activity in Ehrlich ascites carcinoma and P-388 lymphocytic leukemia screens in mice. The N-tosyl chloromethyl ketone analogues prepared from glycine, L-alanine, beta-alanine, L-valine, and 6-(N-tosyl-amino)caproic acid were the most potent antineoplastic agents in the Ehrlich ascites carcinoma screen. The N-tosyl diazomethyl ketone analogues synthesized from glycine, L-leucine, and L-proline were the most active of this series in the Ehrlich ascites screen, along with 5-keto-1-tosyl-2-(diazoacetyl)pyrrolidine and the diazomethyl ketone analogues prepared from 6-(N-tosylamino)caproic acid. In the P-388 lymphocytic leukemia screen, the N-tosyl chloromethyl ketone prepared from glycine and the compound 5-keto-1-tosyl-2-(diazoacetyl)pyrrolidine were the most active.

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Diazomethane; Ketones; Leukemia P388; Male; Mice; Mice, Inbred DBA; Structure-Activity Relationship; Tosyl Compounds

The metabolism of murine tumors sensitive and resistant to 6-theopurines and 5-fluorouracil (5-FU) was studied. A positive correlation between the tumor sensitivity to thiopurines, the level of hypoxanthine-guanine-phosphoribosyl transferase and the rates of the antimetabolite incorporation into RNA and DNA was shown. The sensitivity of tumors to 5-FU correlated with the rates of pyrimidine nucleosides and antimetabolite uptake and the time of retention of labeled 5-FU in RNA. The activites of orotate-phosphoribosyl transferase, uridine kinase, the degree of thymidylate synthetase inhibition of 5-FU and ratio of the de novo to salvage pathways of thymidylate biosynthesis are also important.

Topics: Animals; Antimetabolites, Antineoplastic; Carcinoma, Ehrlich Tumor; Cell Line; Drug Resistance; Fluorouracil; Leukemia L1210; Mercaptopurine; Mice; Neoplasms, Experimental; Purine Nucleotides; Pyrimidine Nucleotides

A series of N-protected cyanomethyl esters of various amino acids was synthesized and tested for antineoplastic and antiinflammatory activity in rodents. Utilizing the L-phenylalanine cyanomethyl ester and varying the N-protecting moiety demonstrated that the N-tosyl and the N-Cbz analogues were the most active against Ehrlich ascites cell proliferation. The N-(carbobenzyloxy)- and N-benzoyl-L-phenylalanine cyanomethyl esters were the most active against carrageenan-induced inflammation. In the N-benzoyl series of cyanomethyl esters, L-alanine, DL-valine, and L-leucine amino acid analogues were the most active against Ehrlich ascites cell proliferation. The glycine and L-alanine analogues possessed the best inhibitor activity in the antiinflammatory screen. The cyanomethyl esters also demonstrated immunosuppressive activity and the ability to suppress the writhing reflex which is associated with inflammatory pain. However, no antipyretic or narcotic analgesic activity was demonstrated by these agents.

Topics: Acetonitriles; Amino Acids; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Body Temperature; Carcinoma, Ehrlich Tumor; Carrageenan; Esters; Immunosuppressive Agents; Lethal Dose 50; Leukemia P388; Male; Mice; Mice, Inbred DBA; Rats; Reaction Time; Structure-Activity Relationship

1,3-Dipolar cycloaddition of benzyl azide or peracetylated glucopyranosyl azides to propargyl halides or 1,4-dihalobutynes yielded 1-benzyl- or 1-glycosyl(halomethyl)-1,2,3-triazoles. Alkylating chloromethyl- bromomethyl- and iodomethyl-1,2,3-triazoles were also obtained from the corresponding hydroxymethyl derivatives by treatment with (C6H5)3P/CCl4, (C6H5O)3P/Br2, and (C6H5O)3P/I2, respectively. 1-Benzyl-4-(fluoromethyl)-1,2,3-triazole was obtained from 1-benzyl-4-(bromomethyl)-1,2,3-triazole by treatment with KF and 18-crown-6. Chloromethyl-, bromomethyl-, and iodomethyl-1,2,3-triazole derivatives inhibited the "in vitro" growth of HeLa cells. Some of these compounds increased the life span of mice bearing tumors.

Topics: Alkylating Agents; Animals; Carcinoma, Ehrlich Tumor; Cell Survival; DNA, Neoplasm; Female; HeLa Cells; Humans; Mice; Nucleosides; Structure-Activity Relationship; Triazoles

Oxidation of N-1 and N-2 alkylbenzotriazoles with m-chloroperbenzoic acid afforded 1-alkylbenzotriazole 3-oxides and 2-alkylbenzotriazole-4,4-diones, respectively. The quinonic compounds inhibited the "in vitro" growth of both HeLa and KB cells, the synthesis of macromolecules (DNA, RNA, and proteins), and the uptake of glucose by Ehrlich carcinoma ascites cells. A possible mode of action is suggested.

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Cell Survival; Cells, Cultured; Chlorobenzoates; DNA; Glucose; Mice; Oxidation-Reduction; Protein Biosynthesis; Quinones; RNA; Triazoles

A series of N-protected vinyl, 1,2-dihaloethyl, and cyanomethyl esters of phenylalanine was synthesized and these compounds were evaluated for antitumor activity against the growth of Ehrlich ascites carcinoma in CF1 male mice (33 mg/kg/day), Walker 256 carcinosarcoma in Sprague-Dawley male rats (2.5 mg/kg/day), and P388 lymphocytic leukemia in DBA/2 mice (20 mg/kg/day). Structure-activity relationships were evaluated and acute toxicity studies (LD50 determinations) in male CF1 mice were also carried out on selected compounds. Carbobenzoxy-L0phenylalanine vinyl ester (5), N-carbobenzoxy-L-phenylalanine 1,2-dibromoethyl ester (12), and N-carbobenzoxy-L-phenylalanine cyanomethyl ester (8) were found to be very potent inhibitors of Ehrlich ascites tumor growth at nontoxic doses cited above. Compounds 5 and 12 also tripled survival time in the Walker 256 system. LD50 values for compounds 5, 12, and 8 were greater than 2000 mg/kg (greater than 6.15 mmol/kg), 74 mg/kg (0.15 mmol/kg), and 150 mg/kg (0.44 mmol/kg), respectively.

Topics: Acetonitriles; Animals; Antineoplastic Agents; Carcinoma 256, Walker; Carcinoma, Ehrlich Tumor; Lethal Dose 50; Leukemia, Experimental; Male; Mice; Mice, Inbred DBA; Phenylalanine; Rats; Vinyl Compounds

Previously reported work on N-protected activated esters of phenylalanine has been extended to include N-protected vinyl, dibromoethyl, and cyanomethyl esters of several other amino acids. These compounds have been synthesized and evaluated in Ehrlich ascites carcinoma, Walker 256 carcinosarcoma, and and P388 lymphocytic leukemia tests. Among compounds tested were derivatives of tyrosine, tryptophan, glycine, leucine, proline, aspartic acid, glutamic acid, 4-aminobutyric acid, and 6-aminocaproic acid. Compounds of greatest potential interest from this study are N-carbobenzoxyglycine 1,2-dibromoethyl ester and N-carbobenzoxy-L-leucine 1,2-dibromoethyl ester. Both compounds were highly active in Ehrlich ascites test systems (33 mg/kg/day). The glycine derivative was also active in the Walker 256 test (2.5 mg/kg/day. Values for LD50's in mice were 148 mg/kg (0.37 mmol/kg) and 225 mg/kg (0.50 mmol/kg) for glycine and leucine derivatives, respectively; therefore, these compounds do not appear to be toxic at effective dose levels.

Topics: Acetonitriles; Amino Acids; Animals; Antineoplastic Agents; Carcinoma 256, Walker; Carcinoma, Ehrlich Tumor; Lethal Dose 50; Leukemia, Experimental; Mice; Structure-Activity Relationship; Vinyl Compounds

Evidence is presented that sesquiterpene lactones or ketones containing the O=CC=CH2 moiety, e.g., tenulin and helenalin, alkylate the thiol group of reduced glutathione and L-cysteine in vitro. A proposal is offered that this mechanism of action is responsible for the observed potent in vivo antitumor activity of these agents in the Ehrlich ascites and Walker 256 carcinosarcoma and to a lesser extent in the P388 leukemic screen. Inhibition of tumor growth is thought to occur due to the O=CC=CH2 system alkylating by rapid Michael addition the SH biological nucleophiles of key regulatory enzymes of nucleic acid and chromatin metabolism. This proposition is in accord with the ability of these agents to inhibit DNA synthesis and gene activity of Ehrlich ascites cells.

Topics: Animals; Antineoplastic Agents, Phytogenic; Ascitic Fluid; Carcinoma 256, Walker; Carcinoma, Ehrlich Tumor; Chromatin; Cyclopentanes; Cysteine; DNA, Neoplasm; Glutathione; Histidine; Lactones; Leukemia, Experimental; Leukemia, Lymphoid; Male; Mice; Mice, Inbred DBA; Neoplasm Proteins; Rats; Sesquiterpenes; Sesquiterpenes, Guaiane; Spectrophotometry, Ultraviolet; Time Factors

Topics: Animals; Brain; Carcinoma, Ehrlich Tumor; Cell Survival; DNA, Neoplasm; Female; Guanine; Kidney; Liver; Mercaptopurine; Mice; Mice, Inbred ICR; Organ Specificity; Structure-Activity Relationship; Xylose

The effect of hydrocortisone on blood-borne tumor metastasis was studied in an i.v. inoculation experiment with Ehrlich hypotetraploid clone 1, Ehrlich hypotetraploid stock, and Ehrlich hyperdiploid stock tumors. The administration of hydrocortisone before tumor inoculation resulted in increased tumor take, reduced mean survival time of mice, and concentration of tumor metastasis in a specific organ (i.e., lung metastasis for Ehrlich hypotetraploid clone 1 tumor, and liver metastasis for Ehrlich hypotetraploid stock and Ehrlich hyperdiploid stock tumors). Enhancement of tumor metastasis, as induced by hydrocortisone pretreatment, was not reproduced by the administration of 6-mercaptopurine, testosterone, or estradiol. The progress of tumor death in hydrocortisone-conditioned mice was not affected by either heparin or dextran sulfate. This indicated that the effect of hydrocortisone on tumor metastasis was independent of the effect of these agents on immune reaction or blood coagulation. In the tracer experiment with 125-I-labeled tumor cells, hydrocortisone pretreatment significantly increased over the control the intrapulmonary retention of Ehrlich hypotetraploid clone 1 tumor cells from 1 through 72 hr after tumor inoculation, the time lag required for the establishment of metastatic foci in the lung. The arrest of Ehrlich hypotetraploid stock and Ehrlich hyperdiploid stock tumors in the liver was also temporarily increased by hydrocortisone pretreatment. No correlation was found between tumor cell size and differential distribution of metastatic tumors with 3 Ehrlich tumors. An attempt was made to use this blood-borne metastasis system for chemotherapeutic study. Administration of cyclophosphamide gave rise to a significant prolongation of survival time and often to complete prevention of tumor metastasis in hydrocortisone-conditioned mice.

Topics: Animals; Carcinoma, Ehrlich Tumor; Cell Line; Cyclophosphamide; Dextrans; Estradiol; Female; Heparin; Hydrocortisone; Injections, Intravenous; Liver Neoplasms; Lung Neoplasms; Mercaptopurine; Mice; Mice, Inbred ICR; Neoplasm Metastasis; Neoplastic Cells, Circulating; Stimulation, Chemical; Testosterone; Time Factors

Topics: Animals; Azaguanine; Carcinoma, Ehrlich Tumor; Clone Cells; Drug Resistance; Guanosine; Injections, Intravenous; Lung; Lung Neoplasms; Mercaptopurine; Methods; Mice; Mice, Inbred ICR; Microspheres; Mutagens; Neoplasm Transplantation; Transplantation, Homologous

Topics: Alkylating Agents; Animals; Antibiotics, Antineoplastic; Ascites; Carcinoma 256, Walker; Carcinoma, Ehrlich Tumor; Drug Resistance; Leukemia L1210; Leukemia, Experimental; Mercaptopurine; Methotrexate; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Piperazines; Piperidines; Transplantation, Homologous

Resistance to adriamycin was developed in an originally adriamycin-sensitive wild strain of Ehrlich ascites tumor (EHR 2) in vivo by treatment with the drug during 25 weekly passages of the tumor. The growth of the resistant line was slower than that of the wild tumor. The resistance was stable for more than 25 weeks both when adriamycin treatment was continued and when treatment was discontinued. The adriamycin-resistant tumor showed cross resistance to daunomycin, just as a daunomycin-resistant subline showed cross resistance to adriamycin. In the adriamycin-resistant tumor, cross resistance to vincristine was also found. There was no change in the sensitivity of the tumor to methotrexate, and it remained nearly insensitive to 6-mercaptopurine, while collateral sensitivity to BCNU and cytosine arabinoside was observed. The data obtained are very similar to data obtained with a daunomycin-resistant line of the same tumor. When adriamycin was given intraperitoneally, it was significantly less toxic than daunomycin, while there was no significant difference in growth-inhibiting effect on the wild Ehrlich ascites tumor.

Topics: Animals; Antibiotics, Antineoplastic; Carcinoma, Ehrlich Tumor; Carmustine; Cytarabine; Dose-Response Relationship, Drug; Doxorubicin; Drug Resistance, Neoplasm; Female; Male; Mercaptopurine; Methotrexate; Mice; Mice, Inbred DBA; Neoplasm Transplantation; Vincristine

Topics: Animals; Antineoplastic Agents; Azoles; Carcinoma, Ehrlich Tumor; Cell Division; Chemical Phenomena; Chemistry; Chlorine; DNA; Ethers, Cyclic; Imidazoles; Mercaptopurine; Mice; Neoplasm Transplantation; Protein Biosynthesis; RNA; Thiadiazoles; Thiazoles

Topics: Animals; Carcinoma, Ehrlich Tumor; Cells, Cultured; Cross Reactions; Cytarabine; Daunorubicin; Dose-Response Relationship, Drug; Doxorubicin; Drug Resistance; Mercaptopurine; Methotrexate; Mice; Nitrosourea Compounds; Vinblastine; Vincristine

Topics: Adenine; Adenine Nucleotides; Animals; Carbon Isotopes; Carcinoma, Ehrlich Tumor; Erythrocytes; Guanine; Humans; Hypoxanthines; Mercaptopurine; Neoplasms; Nucleosides; Nucleotides; Pentosyltransferases; Phosphotransferases; Purines; Pyrimidines; Thioguanine

Topics: Amides; Animals; Carbon Isotopes; Carcinoma, Ehrlich Tumor; Formates; Glycine; Mercaptopurine; Mice; Mice, Inbred Strains; Nucleosides; Osmolar Concentration; Purines; Ribonucleosides; Tritium

Topics: Animals; Carcinoma, Ehrlich Tumor; Cell Division; Cells, Cultured; Depression, Chemical; Female; In Vitro Techniques; Lymphoma; Mercaptopurine; Mice; Mice, Inbred Strains; Time Factors

Topics: Adenosine; Adenosine Diphosphate; Adenosine Triphosphate; Animals; Binding Sites; Carbon Isotopes; Carcinoma, Ehrlich Tumor; Feedback; Kinetics; Mercaptopurine; Phosphotransferases; Protein Binding; Pyrimidines; Pyrroles; Ribonucleosides; Ribonucleotides; Structure-Activity Relationship

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Cell Line; Cyclization; Cyclophosphamide; Cytarabine; Cytidine; Dose-Response Relationship, Drug; Female; Fluorouracil; Leukemia L1210; Leukemia, Experimental; Male; Mercaptopurine; Methotrexate; Mice; Mitomycins; Neoplasms, Experimental; Sarcoma 180

Topics: Animals; Carcinoma, Ehrlich Tumor; Cytarabine; Daunorubicin; Drug Resistance; Female; Injections, Intraperitoneal; Male; Mercaptopurine; Methotrexate; Mice; Neoplasm Transplantation; Nitrosourea Compounds; Time Factors; Vincristine

Topics: Animals; Antimetabolites; Carbon Isotopes; Carcinoma, Ehrlich Tumor; Chromatography; Diphosphates; Drug Synergism; Lymphoma; Male; Mercaptopurine; Mice; Neoplasms, Experimental; Nucleosides; Nucleotides; Pentosephosphates; Ribose

Topics: Animals; Ascitic Fluid; Carcinoma, Ehrlich Tumor; Cell Count; Cyclophosphamide; Male; Mercaptopurine; Mice; Mitomycins; Neoplasm Transplantation; Orotic Acid; Rats; Transplantation, Heterologous; Triazines

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Cyclophosphamide; Fluorouracil; Male; Mercaptopurine; Methotrexate; Mice; Mitomycins; Neoplasm Metastasis; Vinblastine

Topics: Animals; Carbon Isotopes; Carcinoma, Ehrlich Tumor; Drug Synergism; Injections, Intraperitoneal; Mercaptopurine; Mice; Neoplasms, Experimental; Nucleosides; Ribonucleosides; Ribonucleotides; Thioguanine; Time Factors

Topics: Abdomen; Adrenochrome; Aminocaproates; Animals; Carcinoma, Ehrlich Tumor; Clone Cells; Diphenhydramine; Female; Hemorrhage; Hydrocortisone; Karyotyping; Male; Mercaptopurine; Mice; Neoplasm Transplantation; Omentum; Pancreas; Semicarbazides; Time Factors; Virulence

Topics: Adenine; Animals; Carcinoma, Ehrlich Tumor; Cell Membrane; Fluorouracil; In Vitro Techniques; Male; Mercaptopurine; Methotrexate; Mice; Sulfur Isotopes; Time Factors; Tritium; Uracil

Topics: Animals; Aspartic Acid; Bacteriological Techniques; Carcinoma, Ehrlich Tumor; Escherichia coli; Leukemia L1210; Mercaptopurine; Nucleosides; Purines; Pyrimidines; Thiouracil

Topics: Adenine; Animals; Carbon Isotopes; Carcinoma, Ehrlich Tumor; Chromatography, Ion Exchange; Guanine; Liver; Mercaptopurine; Mice; Nucleosides; Nucleotides; Spectrophotometry; Tissue Extracts

Topics: Animals; Antineoplastic Agents; Arabinose; Carcinoma, Ehrlich Tumor; Cell-Free System; Cytosine Nucleotides; Depression, Chemical; Female; Leukemia L1210; Mercaptopurine; Mice; Neoplasms, Experimental; Nucleosides; Nucleotides; Oxidoreductases; Sulfur Isotopes

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Mercaptopurine; Mice; Oxides

Topics: Acridines; Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Carcinoma, Squamous Cell; Cell Division; Culture Techniques; Dactinomycin; Humans; Mercaptopurine; Mice; Nasopharyngeal Neoplasms; Neoplasm Proteins; Seeds

Topics: Animals; Antineoplastic Agents; Azaserine; Busulfan; Carcinoma, Ehrlich Tumor; Colchicine; Culture Techniques; Cyclophosphamide; Depression, Chemical; Diethylstilbestrol; Hydrazines; Immunosuppressive Agents; Mercaptopurine; Methotrexate; Thiotepa; Triaziquone; Urethane

Topics: Animals; Antibody Formation; Carcinoma, Ehrlich Tumor; Diet Therapy; Female; Male; Mercaptopurine; Mice; Neoplasm Regression, Spontaneous; Neoplasm Transplantation; Sarcoma 180; Spleen; Splenectomy; Thiosemicarbazones; Thymectomy; Vitamin B 6 Deficiency

Topics: Animals; Antineoplastic Agents; Ascites; Carcinoma, Ehrlich Tumor; Cyclophosphamide; Electronics, Medical; Mannomustine; Melphalan; Mercaptopurine; Methods; Mice; Sarcoma 180

Topics: Animals; Carcinoma, Ehrlich Tumor; Colorimetry; Depression, Chemical; DNA, Neoplasm; Fluorouracil; Mercaptopurine; Phosphates; Phosphorus Isotopes; RNA, Neoplasm; Spectrum Analysis; Thymidine; Triazines; Tritium; Uracil

Topics: Animals; Antimetabolites; Carcinoma, Ehrlich Tumor; Mercaptopurine; Mice

Topics: Abnormalities, Drug-Induced; Animals; Azaserine; Carcinoma, Ehrlich Tumor; DNA, Neoplasm; Female; Glucosyltransferases; Leukemia L1210; Mammary Neoplasms, Experimental; Mercaptopurine; Mice; Nucleosides; Oxidoreductases; Phosphotransferases; Pregnancy; Pregnancy, Animal; Sarcoma 180; Sarcoma, Experimental

Topics: Adenocarcinoma; Alkylation; Animals; Antimetabolites; Carcinoma, Ehrlich Tumor; Glutamine; Leukemia, Experimental; Leukemia, Radiation-Induced; Mammary Neoplasms, Experimental; Mercaptopurine; Mice; Neoplasm Transplantation; Sarcoma 180

Topics: Animals; Carcinoma, Ehrlich Tumor; Female; Mercaptopurine; Mice; Neoplasm Transplantation; Neoplasms; Sarcoma 180; Thiosemicarbazones; Vitamin B 6 Deficiency

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Busulfan; Carcinoma, Ehrlich Tumor; Fluorouracil; Mechlorethamine; Melphalan; Mercaptopurine; Mice; Nitrogen Mustard Compounds; Uracil

Topics: Acridines; Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Azaguanine; Carcinoma, Ehrlich Tumor; Fluorescence; Male; Mechlorethamine; Mercaptopurine; Mice; Thiotepa

Topics: Animals; Azaserine; Carcinoma, Ehrlich Tumor; Mercaptopurine; Mice; Purines; Pyrimidines

Topics: Adenosine Triphosphate; Animals; Blood Cells; Carcinoma, Ehrlich Tumor; Chromatography, Paper; In Vitro Techniques; Intestinal Mucosa; Liver; Lung; Mercaptopurine; Mice; Nucleotides; Phosphates; Phosphotransferases; Spleen

Topics: Animals; Carcinoma, Ehrlich Tumor; Drug Synergism; Female; Fluorouracil; Glyceraldehyde; Mercaptopurine; Methotrexate; Mice

Topics: Adenine Nucleotides; Animals; Carcinoma, Ehrlich Tumor; Chromatography, Paper; Guanine Nucleotides; In Vitro Techniques; Mercaptopurine; Mice

Topics: Alkylating Agents; Animals; Carcinoma, Ehrlich Tumor; Dactinomycin; Fluorouracil; Hydrocortisone; In Vitro Techniques; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Mechlorethamine; Mercaptopurine; Metabolism; Methotrexate; Mice; Oxidoreductases; Research; Thiotepa; Tissue Culture Techniques; Toxicology

Topics: Animals; Carbohydrate Metabolism; Carcinoma, Ehrlich Tumor; Glucuronidase; Glycosaminoglycans; Hexosamines; Hyaluronoglucosaminidase; Injections, Intraperitoneal; Mercaptopurine; Mice; Mitomycin; Mitomycins; Pharmacology; Research; Thiotepa

1. The formation of adenosine 5'-phosphate, guanosine 5'-phosphate and inosine 5'-phosphate from [8-(14)C]adenine, [8-(14)C]guanine and [8-(14)C]hypoxanthine respectively in the presence of 5-phosphoribosyl pyrophosphate and an extract from Ehrlich ascites-tumour cells was assayed by a method involving liquid-scintillation counting of the radioactive nucleotides on diethylaminoethylcellulose paper. The results obtained with guanine were confirmed by a spectrophotometric assay which was also used to assay the conversion of 6-mercaptopurine and 5-phosphoribosyl pyrophosphate into 6-thioinosine 5'-phosphate in the presence of 6-mercaptopurine phosphoribosyltransferase from these cells. 2. At pH 7.8 and 25 degrees the Michaelis constants for adenine, guanine and hypoxanthine were 0.9 mum, 2.9 mum and 11.0 mum in the assay with radioactive purines; the Michaelis constant for guanine in the spectrophotometric assay was 2.6 mum. At pH 7.9 the Michaelis constant for 6-mercaptopurine was 10.9 mum. 3. 25 mum-6-Mercaptopurine did not inhibit adenine phosphoribosyltransferase. 6-Mercaptopurine is a competitive inhibitor of guanine phosphoribosyltransferase (K(i) 4.7 mum) and hypoxanthine phosphoribosyltransferase (K(i) 8.3 mum). Hypoxanthine is a competitive inhibitor of guanine phosphoribosyltransferase (K(i) 3.4 mum). 4. Differences in kinetic parameters and in the distribution of phosphoribosyltransferase activities after electrophoresis in starch gel indicate that different enzymes are involved in the conversion of adenine, guanine and hypoxanthine into their nucleotides. 5. From the low values of K(i) for 6-mercaptopurine, and from published evidence that ascites-tumour cells require supplies of purines from the host tissues, it is likely that inhibition of hypoxanthine and guanine phosphoribosyltransferases by free 6-mercaptopurine is involved in the biological activity of this drug.

Topics: Adenine; Adenine Nucleotides; Adenosine Monophosphate; Animals; Ascites; Carcinoma, Ehrlich Tumor; Diphosphates; Electrophoresis; Enzyme Inhibitors; Glucosyltransferases; Guanine; Guanine Nucleotides; Hypoxanthines; Kinetics; Mercaptopurine; Nucleotides; Pharmacology; Purines; Research; Spectrophotometry; Transferases; Xanthines

1. A strain of Ehrlich ascites-tumour cells that showed little inhibition of growth in the presence of 6-mercaptopurine accumulated less than 5% as much 6-thioinosine 5'-phosphate in vivo, in the presence of 6-mercaptopurine, as did the sensitive strain from which it was derived. 2. Specific activities of the phosphoribosyltransferases that convert adenine, guanine, hypoxanthine and 6-mercaptopurine into AMP, GMP, IMP and 6-thioinosine 5'-phosphate were similar in extracts of the resistant and the sensitive cells. 3. As found previously with sensitive cells, 6-mercaptopurine is a competitive inhibitor of guanine phosphoribosyltransferase and hypoxanthine phosphoribosyltransferase from the resistant cells and does not inhibit the adenine phosphoribosyltransferase from these cells. Michaelis constants and inhibitor constants of the purine phosphoribosyltransferases from resistant cells did not differ significantly from those measured with the corresponding enzymes from sensitive cells. 4. Resistance to 6-mercaptopurine in this case is probably not due to qualitative or quantitative changes in these transferases.

Topics: Adenine; Adenine Nucleotides; Animals; Ascites; Carcinoma, Ehrlich Tumor; Chromatography; Electrophoresis; Enzyme Inhibitors; Glucosyltransferases; Guanine; Guanine Nucleotides; Humans; Hypoxanthines; Ion Exchange Resins; Kinetics; Mercaptopurine; Metabolism; Nucleotides; Pentosyltransferases; Pharmacology; Research; Xanthines

Topics: Amino Sugars; Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Hexosamines; Hyaluronic Acid; Mechlorethamine; Mercaptopurine; Mice; Mitomycins; Thiotepa

Topics: Alkylating Agents; Animals; Antineoplastic Agents; Azaguanine; Carcinoma, Ehrlich Tumor; Fumarates; Glucuronates; Iron; Mercaptopurine; Mice; Thiotepa

Topics: Alkylating Agents; Animals; Ascorbic Acid; Azaguanine; Carcinoma, Ehrlich Tumor; Chelating Agents; Glucuronates; Hydro-Lyases; Intestinal Absorption; Iron; Mercaptopurine; Mice; Porphyrins; Quinones; Thiotepa

Topics: Animals; Carcinoma, Ehrlich Tumor; Chromatography, Ion Exchange; In Vitro Techniques; Mercaptopurine; Nucleotides; Xanthines

Topics: Animals; Antineoplastic Agents; Arsenic; Carcinoma, Ehrlich Tumor; Cyclophosphamide; Cytostatic Agents; Electron Transport Complex II; Enzyme Inhibitors; Liver; Mannomustine; Mechlorethamine; Mercaptopurine; Metabolism; Mice; Pharmacology; Research; Succinate Dehydrogenase

Topics: Animals; Antimetabolites; Caffeine; Carcinoma; Carcinoma, Ehrlich Tumor; Liver; Mercaptopurine; Metabolism; Mice; Purines; Pyrimidines; Research; Sulfhydryl Compounds; Theobromine; Theophylline

Topics: Alkylating Agents; Amino Acids; Aminolevulinic Acid; Aminopterin; Animals; Antineoplastic Agents; Azaguanine; Blood Chemical Analysis; Carcinoma, Ehrlich Tumor; Catalase; Copper; Folic Acid Antagonists; Hemoglobins; Hydro-Lyases; Iron; Levulinic Acids; Liver; Mercaptopurine; Mice; Neoplasms; Neoplasms, Experimental; Pharmacology; Proteins; Rats; Research

Topics: Animals; Antineoplastic Agents; Antioxidants; Carbon Isotopes; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Leukemia; Leukemia, Experimental; Liver Neoplasms; Mercaptopurine; Neoplasm Proteins; Neoplasms, Experimental; Pharmacology; Proteins; Rats; Research

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Busulfan; Carcinoma, Ehrlich Tumor; Leukemia; Leukemia, Myeloid; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Mice; Neoplasms, Experimental; Nitrogen Mustard Compounds; Olivomycins; Pharmacology; Research; Sarcoma 180; Thiotepa; Toxicology

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Glutaminase; Leukemia; Leukemia, Experimental; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Mice; Neoplasms; Neoplasms, Experimental; Pharmacology; Research; Sarcoma 180; Toxicology

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Heterocyclic Compounds; Mercaptopurine; Mice; Pharmacology; Quinazolines; Rats; Research; Sarcoma 180

Topics: Animals; Anti-Bacterial Agents; Antibodies; Antineoplastic Agents; Blood Cells; Carcinoma, Ehrlich Tumor; Cortisone; Cytarabine; Cytosine; Leukemia L1210; Leukemia, Experimental; Lymphoma; Mercaptopurine; Methotrexate; Mice; Neoplasms; Neoplasms, Experimental; Pharmacology; Research; Sarcoma 180

Topics: Animals; Ascites; Carcinoma; Carcinoma, Ehrlich Tumor; Lactates; Mercaptopurine; Metabolism; Nucleosides; Research; Thioinosine

Topics: Animals; Carcinoma; Carcinoma, Ehrlich Tumor; Chromatography; DNA; DNA, Neoplasm; Glycine; Injections, Intraperitoneal; Mercaptopurine; Metabolism; Mice; Nucleosides; Nucleotides; Pharmacology; Research; RNA; RNA, Neoplasm; Toxicology; Urine

Topics: Adenine Nucleotides; Animals; Ascites; Azaserine; Carcinoma; Carcinoma, Ehrlich Tumor; Chromatography; Histocytochemistry; Mercaptopurine; Metabolism; Mice; Neoplasms, Experimental; Nucleotides; Pharmacology; Phosphoric Monoester Hydrolases; Research

Topics: 5'-Nucleotidase; Animals; Ascites; Carcinoma; Carcinoma, Ehrlich Tumor; Mercaptopurine; Nucleotidases

Topics: Aminopterin; Animals; Antineoplastic Agents; Azaguanine; Carboxylic Acids; Carcinoma, Ehrlich Tumor; Catalase; Cyclopentanes; Liver; Mercaptopurine; Methotrexate; Mice; N-Glycosyl Hydrolases; Neoplasms; Oxidoreductases; Thiotepa; Urate Oxidase; Xanthine Oxidase

Topics: Acridines; Adenine; Animals; Carcinoma; Carcinoma, Ehrlich Tumor; DNA; DNA, Neoplasm; Guanine; Liver; Mercaptopurine; Mice; Neoplasms; Nucleotides; Pharmacology; Proteins; Research

Topics: Animals; Biosynthetic Pathways; Carbon Isotopes; Carcinoma; Carcinoma, Ehrlich Tumor; DNA; DNA, Neoplasm; Formates; Glycine; Leukemia L1210; Mercaptopurine; Metabolism; Nucleotides; Purines; Research; RNA; RNA, Neoplasm; Sarcoma 180

Topics: Alkylating Agents; Animals; Antineoplastic Agents; Azaguanine; Azaserine; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; DNA; DNA, Neoplasm; Fluorouracil; Idoxuridine; Liver Neoplasms; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Mice; Neoplasms, Experimental; Nitrogen Mustard Compounds; Nucleosides; Nucleotides; Purines; Research; RNA; RNA, Neoplasm; Sarcoma 180; Thioguanine; Uracil Mustard

Topics: Animals; Antineoplastic Agents; Arsenicals; Carbamates; Carcinoma; Carcinoma, Ehrlich Tumor; Colchicine; Dactinomycin; Diethylstilbestrol; Enzyme Inhibitors; Fluorouracil; Hydrocortisone; In Vitro Techniques; Mechlorethamine; Mercaptopurine; Methotrexate; Mice; Oxidoreductases; Research; Thalidomide; Thiotepa

Topics: Animals; Antimetabolites; Biochemical Phenomena; Carcinoma; Carcinoma, Ehrlich Tumor; Glucosyltransferases; Mercaptopurine; Metabolism; Nucleosides; Nucleotidases; Nucleotides; Nucleotidyltransferases; Pharmacology; Research

Topics: Animals; Antineoplastic Agents; Ascites; Azaserine; Carcinoma, Ehrlich Tumor; Humans; Mercaptopurine; Neoplasms, Experimental; Pyrimidines; Thioguanine

Topics: Animals; Antineoplastic Agents; Ascites; Carcinoma, Ehrlich Tumor; Humans; Mercaptopurine; Purines; Sulfhydryl Compounds

Topics: Animals; Ascites; Azaserine; Azoles; Carcinoma, Ehrlich Tumor; Humans; Mercaptopurine; Neoplasms; Neoplasms, Experimental; Pyrimidines; Serine; Thioguanine

Topics: Animals; Carcinoma, Ehrlich Tumor; Diploidy; Mercaptopurine; Neoplasms, Experimental

Topics: Animals; Ascites; Carcinoma, Ehrlich Tumor; Mercaptopurine; Neoplasms; Phosphates

Topics: Animals; Anti-Bacterial Agents; Ascites; Azaserine; Carcinoma, Ehrlich Tumor; Mercaptopurine; Neoplasms; Purines