melphalan and Carcinoma-256--Walker

A 14C study of chemobiokinetics of sarcolysin and its peptides of glutaminic acid, dosage and routes of administration was conducted in intact rats and those bearing Walker's carcinoma. Similar in shape for peptides, kinetic curves differed from those found for sarcolysin. The rates of absorption and excretion of sarcolysin peptides in intraperitoneal and, particularly, oral administration were lower than those of sarcolysin. Tumor appeared to play a role in a higher rate of peptide excretion. While sarcolysin and its peptides distribution in organs and tissues was generally identical, time of peak radioactive concentration build-up was different. Time needed for accumulation and excretion of peptides from tumor was much longer than from other organs or tissues. Sarcolysin went chiefly to urine while peptides--to faeces.

Topics: Administration, Oral; Animals; Antineoplastic Agents, Alkylating; Area Under Curve; Carbon Radioisotopes; Carcinoma 256, Walker; Drug Administration Schedule; Glutamates; Infusions, Parenteral; Male; Melphalan; Peptides; Rats; Time Factors; Tissue Distribution

Melphalan, a nitrogen mustard derivative of the neutral amino acid L-phenylalanine, was transported across the rat blood-brain barrier by the large (L-system) neutral amino acid transporter in tumor-bearing brain, but no evidence for blood-brain barrier transport by the alanine-serine-cysteine system carrier was obtained in the present study. The ability of melphalan to inhibit phenylalanine uptake was compared in rats implanted with two experimental CNS tumors: the C-6 glioma (a model of primary brain tumors) and Walker carcinoma (a model of metastatic brain tumors). The melphalan concentration which caused 50% inhibition of blood-brain barrier (BBB) phenylalanine uptake (Ki) was 0.49 +/- 0.18 mM in the Walker tumor, compared with 0.46 +/- 0.19 mM in the contralateral control brain. In the ipsilateral hemisphere (Ki = 0.59 +/- 0.25 mM) and contralateral hemisphere (Ki = 0.45 +/- 0.19 mM), drug entry was also via the neutral amino acid transporter. In C-6 gliomas (Ki = 0.77 +/- 0.20 mM) and contralateral control brain (Ki = 0.84 +/- 0.29 mM), melphalan also inhibited BBB phenylalanine transport. A major finding was that, at melphalan concentrations greater than 1.0 mM, BBB permeability of radiolabeled indium (chelated to EDTA) increased in proportion to melphalan concentration. In the contralateral hemisphere of rats implanted with C-6 gliomas, brain extractions of indium-EDTA measured 3 to 4% in the absence of drug, 5 to 6% at 2.5 mM melphalan, and 9 to 10% at 5 mM melphalan. A similar phenomenon was observed in the nontumoral brain regions of rats implanted with Walker carcinoma cells. In normal (nonimplanted) rats, melphalan's inhibition (Ki = 0.29 mM) of phenylalanine and tryptophan (Ki = 0.20 mM) uptake was confirmed, and brain extraction of sucrose (a nonspecific marker which does not penetrate the intact BBB) was observed to increase in proportion to melphalan concentration. We conclude that melphalan not only enters the brain via the neutral amino acid transporter, but at higher concentrations (greater than 1 mM) may open the blood-brain barrier in a nonspecific manner.

Topics: Amino Acid Transport Systems; Animals; Biological Transport; Blood-Brain Barrier; Carcinoma 256, Walker; Carrier Proteins; Melphalan; Phenylalanine; Rats

Several cell lines resistant to alkylating agents possess increased activity of glutathione-S-transferase (GST) drug detoxifying enzymes. Inhibition of certain enzymes of the glutathione redox system may affect cellular sensitivity to alkylators. We report that the (-.)enantiomer of gossypol is a potent and selective inhibitor of GST alpha and GST pi isozymes, and that in combination with buthionine sulfoximine (BSO), causes the enhanced modulation of alkylator resistance in two drug resistant cell lines with increased GST activity. The use of (-)gossypol alone had no effect on the 2-5-fold resistance of MCF-7 Adr and Walker resistant cells to chlorambucil, melphalan and BCNU. Cellular depletion of glutathione with BSO resulted in a 2-4-fold modulation of cell sensitivity to these alkylators. However, the combination of (-)gossypol with BSO resulted in a markedly greater modulation of alkylator sensitivity than with either inhibitor alone. Therefore, the complementary inhibition of glutathione and GST by BSO and (-)gossypol, respectively, produced a synergistic modulation of alkylator cytotoxicity in these drug resistant cell lines. The favorable clinical pharmacokinetics of (-)gossypol suggest its further evaluation for use in combination with BSO and alkylating agents in clinical trials.

Topics: Alkylating Agents; Animals; Breast Neoplasms; Buthionine Sulfoximine; Carcinoma 256, Walker; Carmustine; Cell Division; Cell Line; Chlorambucil; Cisplatin; Drug Antagonism; Drug Resistance; Glutathione Transferase; Gossypol; Humans; In Vitro Techniques; Isomerism; Melphalan; Methionine Sulfoximine; Rats

Equimolar doses of chlorambucil and melphalan (both 10 mg/kg) were administered i.v. to anesthetized rats, and the plasma and brain concentrations of chlorambucil, its metabolites 3,4-dehydrochlorambucil and phenylacetic mustard, and melphalan were determined by high-performance liquid chromatography from 5 to 240 min thereafter. Chlorambucil demonstrated a monophasic disappearance from plasma, with a half-life of 26 min. The compound was 99.6% plasma-protein-bound. Chlorambucil underwent beta-oxidation to yield detectable concentrations of 3,4-dehydrochlorambucil and substantial amounts of phenylacetic mustard in the plasma. Low concentrations of chlorambucil and phenylacetic mustard were detected in the brain. Calculated from the areas under the concentration-time curves, the brain:plasma concentration integral ratios of chlorambucil and phenylacetic mustard were 0.021 and 0.013, respectively. Melphalan demonstrated a biphasic disappearance from plasma, with half-lives of 1.9 and 78 min. The compound was approximately 86% plasma protein-bound. Low concentrations of melphalan were detected in the brain, and its brain:plasma ratio was 0.13. These data demonstrate that following the administration of chlorambucil and melphalan, only low concentrations of active drug are able to enter the brain. As a consequence, concentrations of both drugs that cause the complete inhibition of extracerebrally located tumor have no effect on those located within the brain. Further, the brain uptake of melphalan, although low, is greater than that of chlorambucil and its active metabolites, which coincides with its slightly greater intracerebral activity following the systemic administration of very high doses.

Topics: Amino Acids; Animals; Blood Proteins; Brain; Carcinoma 256, Walker; Chlorambucil; Half-Life; Male; Melphalan; Protein Binding; Rats

The aim of this study was to investigate whether the newly synthesized bisphosphonic acid-linked N-Lost derivative BAD retains bone-seeking and cytostatic properties. The paper describes experiments on mutagenicity in vitro and on toxicity in vivo. BAD is characterized by very low mutagenic activity toward histidine auxotrophic Salmonella typhimurium strains. Cytotoxic effects were tested in rat osteosarcoma and in Walker carcinosarcoma 256B. The LD50 of i.v. injected BAD was 146 mg/kg. Acute toxicity is probably caused by calcium complexing of the bisphosphonate part of the molecule. Labeling experiments showed moderate accumulation in bone and osteosarcoma, as well as in lung metastases. BAD effected high tumor growth inhibition in osteosarcoma and Walker carcinosarcoma-bearing rats and marked prolongation of survival; histologic and radiographic examination revealed rapid calcification of osteosarcoma and lung metastases. BAD-pretreatment produced protective effects against osteolysis induced by intratibially implanted Walker carcinosarcoma ascites cells. The cytostatic efficacy of equitoxic doses of BAD in rat osteosarcoma is comparable to that of dacarbazine and in Walker carcinosarcoma to that of melphalan.

Topics: Animals; Antineoplastic Agents; Body Temperature; Body Weight; Bone and Bones; Bone Development; Bromine; Calcium; Carcinoma 256, Walker; Diphosphonates; Dose-Response Relationship, Drug; Female; Kidney; Male; Melphalan; Mice; Mice, Inbred Strains; Mutagens; Nitrogen Mustard Compounds; Osteosarcoma; Pamidronate; Radioisotopes; Rats; Rats, Inbred Strains; Salmonella typhimurium; Sex Factors; Tissue Distribution

In rats with transplantable Walker carcinosarcoma the injection of sarcolysin is found to retard a fall in the adrenaline concentration in adrenal tissues, observed without the substance. Normalization of the adrenaline level proceeds against the background of variations in the noradrenaline concentration near and above control values. Injecting of sarcolysin in intact animals results in normalization of the adrenaline level against the background of a considerable fall in the noradrenaline concentration after each injection of the drug. Changes of the same character were also observed in case of injecting saline solution in intact animals, the only difference being due to the fact that the effect of sarcolysin is dependent on animals age, while that of saline solution is not.

Topics: Adrenal Glands; Age Factors; Animals; Carcinoma 256, Walker; Epinephrine; Male; Melphalan; Norepinephrine; Rats; Sodium Chloride

Topics: Animals; Carcinoma 256, Walker; Cell Survival; Chlorambucil; Flurbiprofen; Hematopoietic Stem Cells; Indomethacin; Melphalan; Mice; Propionates

The antitumor effect of some N alpha-benzyloxycarbonyl-N,N-bis-(2-halogenethyl)hydrazide derivatives of lysine, glycine, cystine, phenylalanine and p-chlorophenylalanine, was studied. Six of eight newly synthesized compounds show considerable antitumor effect on solid Walker carcinosarcoma 256 (about 95% tumor growth inhibition). Three of these compounds under study increased the lifespan of mice with leukemia L1210. The investigation of the effect of N alpha-benzyloxycarbonyl,D,L-phenylalanine-N,N-bis(2-chloroethyl)hydrazine on various mouse tumors showed remarkable growth inhibition of the Ehrlich ascites carcinoma, sarcoma 37, colon adenocarcinoma akatol and lesser antitumor effect also on solid adenocarcinoma 755, Lewis lung carcinoma and melanoma B16. All investigated compounds exhibited depression of leukocyte count--their toxicity being, however, lower than that of sarcolysine in parallel experiments.

Topics: Amino Acids; Animals; Antineoplastic Agents; Carcinoma 256, Walker; Hematopoietic System; Hydrazines; Leukemia L1210; Leukocyte Count; Melphalan; Mice; Neoplasms, Experimental; Nitrogen Mustard Compounds; Rats

Comparison is made of the development of resistance to cyclophosphamide (CPA) and L-phenylalanine mustard (L-PAM), of cross-resistance, and chromosome counts, in Walker 256 (W256), rat sarcoma R3 (R3), leukemia L1210, and Ridgway osteogenic sarcoma. For development of resistance the single maximum tolerated doses of CPA or L-PAM were used, each for two sublines in the four tumors. In W256 after only one to five treatment generations, all sublines were resistant, whereas only by generation 10 had R3/CPA, R3/L-PAM, and L1210/CPA reached marked resistance, and L1210/L-PAM reached moderate resistance. All four Ridgway osteogenic sarcoma sublines were essentially still as sensitive as the parent tumor. Long-established resistant sublines from previous studies (greater than 20 treatment generations) were used for cross-resistance, chromosome, and stability studies. All W256-resistant sublines were cross-resistant to CPA, L-PAM, and thiotepa; but the sublines of the other tumors, although showing marked, or in the case of L1210/CPA, complete resistance to their respective inducing agents, retained moderate-to-full sensitivity to the other alkylators. W256/CPA and W256/L-PAM were mainly polyploid (greater than 80% of cells), whereas the other tumors were mainly diploid or near diploid. During 10 to 20 untreated generations the degree of drug resistance remained unchanged in W256 and L1210 lines, but was reduced in R3 and Ridgway osteogenic sarcoma lines. The resistance pattern of W256 appears to be compatible with a simple selection mechanism, whereas those of the three other tumors suggest involvement of multiple determinants. This study suggests that some, but not all, tumors have universal cross-resistance between different types of alkylating agents.

Topics: Animals; Carcinoma 256, Walker; Cyclophosphamide; Drug Resistance; Female; Karyotyping; Leukemia L1210; Melphalan; Mice; Neoplasms, Experimental; Rats

Topics: Animals; Bone Marrow; Carcinoma 256, Walker; Chlorambucil; Digestive System; Flurbiprofen; Indomethacin; Melphalan; Mice; Propionates; Rats

Topics: Alkylating Agents; Animals; Carcinoma 256, Walker; Cells, Cultured; Chemical Phenomena; Chemistry; Ethylenediamines; Lactams; Leukemia, Experimental; Male; Mice; Rats; Sesquiterpenes; Sesquiterpenes, Guaiane

Several new cyclopentenones related to helenalin have been synthesized as potential alkylating antitumor agents. The procedure involved the transformation of 2-methyl-2-carbethoxycyclopentanone (2) to an ethylene ketal 3, bromination of 3 followed by dehydrobromination to yield a ketal olefin 5, reduction of 5 to the alcohol 6, conversion of 6 to the corresponding hydroxycyclopentenone 7, and estrification of 7 to afford the cyclopentenone esters 8--11. Biological assays indicated that only cyclopentenones possessing a conjugated ester side chain, such as 9 and 10, demonstrated significant in vitro cytotoxicity against the growth of tissue culture cells originating from human epidermoid carcinoma of the larynx (H.Ep.-2) as well as in vivo antitumor activity in Walker 256 carcinosarcoma in rats and P-388 lymphocytic leukemia in mice.

Topics: Animals; Antineoplastic Agents, Phytogenic; Carcinoma 256, Walker; Cells, Cultured; Cyclopentanes; Leukemia, Experimental; Leukemia, Lymphoid; Male; Mice; Mice, Inbred DBA; Rats; Sesquiterpenes; Sesquiterpenes, Guaiane

Topics: Animals; Antineoplastic Agents; Caffeine; Carcinoma 256, Walker; Cells, Cultured; Drug Synergism; Lymphoma; Mechlorethamine; Melphalan; Rats; Time Factors

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

Uracil and thymine alpha-methylene-gamma-lactones and related derivatives have been synthesized as novel potential alkylating antitumor agents. The synthesis of these compounds involved the convenient Reformatsky-type reaction between ethyl-alpha-(bromomethyl)acrylate and the proper pyrimidinyl ketones. Preliminary in vivo tumor assay indicated that these compounds were active against the Walker 256 carcinosarcoma in rats and the P-388 lymphocytic leukemia as well as the B-16 melanotic melanoma in mice at 2.5-25 mg/kg.

Topics: Animals; Antineoplastic Agents; Carcinoma 256, Walker; Lactones; Leukemia, Experimental; Male; Melanoma; Mice; Neoplasms, Experimental; Rats; Thymine; Uracil

Centrophenoxine, without antitumor activity itself, enhanced the cytotoxic action of melphalan and "activated" cyclophosphamide against mouse P388 lymphoma and rat W256 carcinosarcoma cells growing in static suspension culture. The concentration of alkylating agent required for 99% cell-kill was approximately halved when centrophenoxine was also present during exposure to the antitumor drug. Maximum potentiation by centrophenoxine of the cytotoxic action of melphalan occurred when cells were exposed to the two agents simultaneously; little or no potentiation was observed when cells were exposed to centrophenoxine before or after exposure to the alkylating agent.

Topics: Animals; Antineoplastic Agents; Carcinoma 256, Walker; Cell Division; Cells, Cultured; Chlorpromazine; Cyclophosphamide; Drug Synergism; Glycolates; In Vitro Techniques; Lymphoma; Meclofenoxate; Melphalan; Neoplasms, Experimental; Time Factors

Topics: Animals; Aziridines; Azirines; Biological Assay; Biological Transport, Active; Carcinoma 256, Walker; Cell Survival; DNA Replication; DNA, Neoplasm; Drug Antagonism; Glucose; Imidazoles; Melphalan; Neoplasm Proteins; Protein Biosynthesis; Rats; RNA, Neoplasm; Transcription, Genetic

Topics: Alkylating Agents; Animals; Carcinoma 256, Walker; Cells, Cultured; Chlorambucil; Cyclic AMP; Drug Resistance; Electrophoresis; Female; Kinetics; Lymphoma; Male; Melphalan; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Neoplasm Proteins; Neoplasm Transplantation; Neoplasms, Experimental; Phosphoric Diester Hydrolases; Plasmacytoma; Rats; Time Factors; Transplantation, Homologous

Topics: Ampyrone; Animals; Antineoplastic Agents; Antipyrine; Carcinoma 256, Walker; Drug Evaluation, Preclinical; Female; Lethal Dose 50; Leukemia, Experimental; Male; Melphalan; Mice; Nitrogen Mustard Compounds; Rats; Sarcoma 180

Topics: Animals; Antineoplastic Agents; Aziridines; Carcinoma 256, Walker; Cyclophosphamide; Fluorouracil; Melphalan; Methotrexate; Nitrofurans; Nitrogen Mustard Compounds; Organophosphorus Compounds; Rats; Rats, Inbred Strains; Species Specificity; Thiotepa

Topics: Animals; Antineoplastic Agents; Carcinoma 256, Walker; Carcinoma, Ehrlich Tumor; Female; Leukemia, Experimental; Leukocyte Count; Lymphoid Tissue; Male; Mammary Neoplasms, Experimental; Melphalan; Mice; Mice, Inbred C3H; Neoplasm Transplantation; Neoplasms, Experimental; Organ Size; Ovarian Neoplasms; Rats; Sarcoma 180; Sarcoma 37; Sarcoma, Experimental; Spleen; Splenic Neoplasms; Thymus Gland; Thymus Neoplasms; Time Factors; Triazines

Topics: Alkylating Agents; Animals; Azirines; Benzamides; Carcinoma 256, Walker; Cell Line; Depression, Chemical; DNA, Neoplasm; Melphalan; Mice; Neoplasm Proteins; Nitro Compounds; Purines; Rats; RNA, Neoplasm; Thymidine; Time Factors; Tritium; Uridine

Topics: Adenocarcinoma; Alkylating Agents; Animals; Antibodies, Neoplasm; Antibody Formation; Antibody Specificity; Carcinoma 256, Walker; Carcinoma, Squamous Cell; Carrier Proteins; Colonic Neoplasms; Esophageal Neoplasms; Haptens; Hemagglutination Tests; Humans; Immune Sera; Immunization; Immunodiffusion; Immunoelectrophoresis; Melphalan; Rabbits; Rats; Species Specificity

Topics: Animals; Carcinoma 256, Walker; Carrier Proteins; Haptens; Hydrocortisone; Immune Sera; Immunization, Passive; Immunosuppressive Agents; Injections; Injections, Intramuscular; Injections, Intravenous; Male; Melphalan; Rats; Rats, Inbred Strains

Topics: Animals; Carcinoma 256, Walker; Cytarabine; DNA, Neoplasm; Drug Resistance; Female; Male; Melphalan; Methylcholanthrene; Mice; Neoplasm Transplantation; Rats; Sarcoma, Experimental; Spectrophotometry; Transplantation, Homologous; Tritium; Vinblastine

Topics: Animals; Antibody Specificity; Carcinoma 256, Walker; Haptens; Hindlimb; Immune Sera; Immunization, Passive; Immunotherapy; Melphalan; Neoplasm Regression, Spontaneous; Neoplasm Transplantation; Rats; Transplantation, Homologous

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Carcinoma 256, Walker; Dactinomycin; Fluorouracil; Melphalan; Mercaptopurine; Methylthiouracil; Mice; Mice, Inbred Strains; Neoplasm Transplantation; Neoplasms, Experimental; Nitrogen Mustard Compounds; Rats; Sarcoma, Experimental; Time Factors

Topics: Animals; Antineoplastic Agents; Carcinoma 256, Walker; Cyclophosphamide; Evaluation Studies as Topic; Melphalan; Rats; Sarcoma, Experimental; Statistics as Topic; Thiotepa

Topics: Animals; Carcinoma 256, Walker; Carcinoma, Ehrlich Tumor; Creatinine; Female; Leukemia L1210; Male; Melanoma; Melphalan; Mice; Mice, Inbred Strains; Neoplasm Transplantation; Neoplasms, Experimental; Rats; Sarcoma 180; Sarcoma, Experimental; Serotonin

The rat Walker 256 tumour was grown in mice that had previously been thymectomized and treated with anti-lymphocyte serum. These rat tumour-bearing mice were used to determine the therapeutic indices of 4 anti-tumour drugs.The agent with the highest index of the four examined was 5-aziridino 2,4-dinitrobenzamide (CB1954), followed by melphalan, aniline mustard and methotrexate, in that order. This rank order is the same as that found when therapeutic indices are determined on the Walker tumour growing in the rat. In this system, therefore, drugs have been ranked correctly in effectiveness against a rat tumour by measuring their effects on the tumour when growing in an immunosuppressed xenogeneic species. The implications for testing the drug sensitivity of individual human tumours before treating the patient are discussed.

Topics: Animals; Antilymphocyte Serum; Antineoplastic Agents; Azirines; Benzoates; Carcinoma 256, Walker; Immunosuppression Therapy; Lethal Dose 50; Melphalan; Methotrexate; Mice; Neoplasm Transplantation; Nitro Compounds; Nitrogen Mustard Compounds; Rats; Thymectomy; Transplantation, Heterologous

Topics: Alkylating Agents; Animals; Azirines; Benzoates; Carcinoma 256, Walker; Cell Fusion; Culture Techniques; Depression, Chemical; Hybridization, Genetic; Melphalan; Nitro Compounds; Pharmacogenetics; Rats

Topics: Animals; Azirines; Benzoates; Carcinoma 256, Walker; DNA, Neoplasm; In Vitro Techniques; Male; Melphalan; Mice; Rats; RNA, Neoplasm; Tritium

Topics: Adenocarcinoma; Animals; Carcinoma 256, Walker; Chlorambucil; Cyclophosphamide; Melphalan; Mercaptopurine; Mice; Neoplasms, Experimental; Sarcoma, Experimental

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antiviral Agents; Ascites; Carcinoma 256, Walker; Carcinoma, Ehrlich Tumor; Cyclophosphamide; Depression, Chemical; Injections, Intraperitoneal; Injections, Subcutaneous; Leukemia, Experimental; Mechlorethamine; Melphalan; Mice; Neoplasms, Experimental; Nitrogen Mustard Compounds; Rats; Sarcoma; Sarcoma 180; Thiotepa; Uracil

Topics: Animals; Carcinoma 256, Walker; Carcinoma, Ehrlich Tumor; Female; Leukopenia; Lung Neoplasms; Lymphoma, Non-Hodgkin; Melphalan; Mice; Neoplasm Metastasis; Ovarian Neoplasms; Peritoneal Neoplasms; Rats; Sarcoma 180; Sarcoma, Experimental; Thiotepa; Triazines

Topics: Alkylating Agents; Animals; Benzopyrenes; Carcinoma 256, Walker; Carcinoma, Hepatocellular; Female; Fibrosarcoma; Hematopoietic System; Kidney; Leukemia L1210; Liver; Liver Neoplasms; Male; Melphalan; Mice; Neoplasms; Neoplasms, Experimental; Nitrogen Mustard Compounds; Plasmacytoma; Rats; Sarcoma, Experimental; Sarcoma, Yoshida

Topics: Amino Acids; Animals; Antineoplastic Agents; Carcinoma 256, Walker; Chemical Phenomena; Chemistry; Fluorescence; Melphalan; Peptides; Rats

Topics: Acetates; Animals; Antineoplastic Agents; Azirines; Benzene; Benzoates; Butyrates; Carcinoma 256, Walker; Glycine; Mannitol; Mechlorethamine; Melphalan; Niacinamide; Oxides; Phthalic Acids; Pyridines; Rats; Sulfhydryl Compounds; Toluene; Xylenes

Topics: Animals; Blood Protein Electrophoresis; Carcinoma 256, Walker; Cyclophosphamide; Glucuronidase; Melphalan; Mice; Mitomycins; Multiple Myeloma; Neoplasm Proteins; Neoplasm Transplantation; Neoplasms, Experimental; Nitrogen Mustard Compounds; Transplantation Immunology; Urethane

Topics: Animals; Bone Marrow; Carcinoma 256, Walker; Chromatography; DNA; Intestines; Kidney; Liver; Melphalan; Metabolism; Muscles; Mustard Plant; Neoplasms; Pharmacology; Phenylalanine; Plasma; Rats; Research; Spleen; Thymus Gland; Tritium; Tyrosine

Topics: Animals; Carcinoma 256, Walker; DNA; DNA, Neoplasm; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Melphalan; Mice; Neoplasms; Neoplasms, Experimental; Pharmacology; Phosphorus Isotopes; Rats; Research; RNA; RNA, Neoplasm; Sarcoma; Sarcoma, Yoshida; Tissue Culture Techniques

Topics: Animals; Carcinoma; Carcinoma 256, Walker; Dipeptides; Melphalan; Mice; Nitrogen Mustard Compounds; Pharmacology; Rats; Research; Sarcoma, Experimental

Topics: Animals; Antineoplastic Agents; Carcinoma 256, Walker; Carcinoma, Ehrlich Tumor; Carcinoma, Krebs 2; Feeding and Eating Disorders; Leukopenia; Melanoma; Melphalan; Neoplasms; Neoplasms, Experimental; Pharmacology; Research; Sarcoma; Sarcoma, Experimental

Topics: Animals; Carcinoma; Carcinoma 256, Walker; Chemistry, Pharmaceutical; Leukemia L1210; Melphalan; Mice; Nitrogen Mustard Compounds; Peptides; Pharmacology; Phenylalanine; Rats; Research; Sarcoma 180; Toxicology

Topics: Alkylating Agents; Animals; Antineoplastic Agents; Carcinoma 256, Walker; Carcinoma, Hepatocellular; Chemistry, Pharmaceutical; Leukemia; Leukemia, Experimental; Liver Neoplasms; Lung Neoplasms; Melphalan; Neoplasms, Experimental; Nitrogen Mustard Compounds; Pharmacology; Phenylalanine; Research; Skin Neoplasms