Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calculated and observed log P values are reported and compared with in vivo and in vitro biological action (L1210 leukemia ILS % and ribonucleotide reductase ID50) for hydroxyurea, the 1-N methyl and ethyl, and the 3-N ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, phenyl, and p-chlorophenyl analogues. The log P values were calculated via the method of Hansch and Leo from literature f values and the observed log P values were obtained by direct determination after equilibration between octanol and water. Calculations of log P for hydroxyurea were found to be appreciably more hydrophilic than the values obtained experimentally. Differences in calculated and observed log P (delta log P) for the substituted analogues were lowest with the 1-N and the bulky 3-N substituents and greatest with the 3-N-substituted straight-chain analogues (delta log P = 0.70). Different structural species were observed by infrared spectroscopy in dry octanol vs. octanol after water equilibration and drying, and this is proposed as due to changes in conformational equilibrium in the hydroxyurea systems. Differences between calculated and observed log P are explained via the stabilization of internally hydrogen-bonded conformers in the case of 1-N or bulky 3-N analogues or destabilization of various conformers allowing maximal interactions with solvent or water which is the case with straight chain 3-N analogues.
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PMID:Effect of the solvent-dependent conformational system of hydroxyureas on predicted vs. observed log P. 92 24

Four nonabsorbable antibiotics (streptomycin, neomycin, bacitracin, and amphotericin B) and a germicidal dip solution (Zephiran chloride/water) were used to eliminate all the detectable bacteria from conventional AKR mice. Control mice were not decontaminated and were used as such. When antibiotic-decontaminated and control mice developed clinical manifestations of spontaneous lymphatic leukemia, each was treated for the disease with an antitumor drug (cyclophosphamide [CP]) at weekly intervals. With the decontamination procedure, mice of each of the two groups became bacteria-free after 16 weeks of continuous oral administration of the antibiotics and two separate germicidal dippings. All decontaminated mice remained free of bacteria throughout the experiment. The bacterial flora of the control mice remained unaltered. With CP therapy, the mean survival time of the female decontaminated mice was 65 days, whereas that of male mice was 218 days. The average survival time of the CP-treated control leukemic mice was 51 days. Untreated decontaminated or control mice usually died of leukemia within 7 days after the onset of symptoms of leukemia. Although CP therapy was not curative, it did prolong the life expectancy of the decontaminated mice significantly.
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PMID:Bacterial decontamination and antileukemic therapy of AKR mice. 97 25

Three groups of Donryu rats, each consisting of 36 females, were continuously given solutions of 1-butyl-3,3-dimethyl-1-nitrosourea as drinking water (400 ppm for group A, 200 ppm for group B 100 ppm for group C). Of the 100 rats that survived at least 122 experimental days, 64 developed leukemia and 38 had vaginal tumors. Leukemias were preponderant in animals of groups A and B; vaginal tumors appeared in group C.
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PMID:Leukemias and vaginal tumors induced in female Donryu rats by continuous administration of 1-butyl-3,3-dimethyl-1-nitrosourea in the drinking water. 99 20

A series of 15 2,5-diaziridinyl-3,6-bis(alkylamino)-1,4-benzoquinone derivatives was synthesized and evaluated as central nervous system antitumor agents in the murine intracerebral L1210 and ependymoblastoma brain tumor systems. Intraperitoneal activity was evaluted in the leukemia L1210, P388, and B16 melanocarcinoma tumor models. The more hydrophilic hydroxyalkylamino compounds were the most effective in the intraperitoneal ascites systems (L1210, P388) with the dihydroxypropylamino (18) and hydroxyethylamino (17) analogues producing long-term survivors. The simple, more lipophilic mono- and dialkylamino derivatives were most effective in the intracerebral systems. Multiple long-term survivors were obtained with the methyl (13), ethyl (14), and dimethylamino (20) compounds in the ependymoblastoma brain tumor system. The parent amino analogue 12 was very active in several tumor models. The relationship between structure, activity, and water solubility are discussed.
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PMID:Potential central nervous system antitumor agents. Aziridinylbenzoquinones. 100 7

The erythroblastic leukemia produced in Long-Evans rats by the administration of 7, 8, 12 trimethylbenz (a) anthracene has been used as a model of the most immature form of the erythrocyte series. In conjunction with studies of the maturation of several other membrane functions, the permeability of this cell to water and to certain definitive non-electrolytes was measured with osmotic methods. The hydraulic conductivity, L-p was 6.2 micro (minute)-1, (atm)-1 at 25 degrees C, quite high and characteristic of mature erythrocytes, but different from values of 0.65 for immature myeloid cells. The effect of temperature provided an energy of activation of 4.4 kCal/mole, also typical of mature mammalian erythrocytes but again different from 13 to 18 kCal/mole for immature myeloid cells. Urea was compared to thiourea. The permeability coefficient for urea was 76.7 micra (minute)-1 plus or minus 13.8 (S. E.); the value for thiourea was 1.55 micra (minute)-1 plus or minus 0.18 (S. E.). Phloretin at 0.25 mM inhibited urea permeability by 90% with 50% inhibition occurring at 0.05 mM. Inhibition was reversible. Permeability to the glycols was also compatible with mature erythrocytes. We infer from these findings that the structure which underlies these basic, passive membrane functions is laid down early and persists after loss of nucleus and subsequent maturation.
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PMID:Maturation of membrane function: the permeability of the rat erythroblastic leukemic cell to water and to non-electrolytes. 105 96

Three groups of female Donryu rats were continuously given 600, 300, or 150 ppm solution of 1-propyl-1-nitrosourea in their drinking water. Leukemias developed in 62 of 109 (57%) rats surviving for more than 17 weeks and tumors developed in the digestive tracts of 31 (28%) animals. Of the leukemias, the differentiated myelocytic type was the most frequent, followed by myeloblastic leukemia and erythroleukemia. Tumors in the digestive tract, predominantly in the glandular stomach and duodenum, were both epithelial and nonepithelial. The other induced tumors were mainly in the mammary glands, ear ducts, and thymus, though the incidence was less than 15%.
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PMID:Induction of Leukemias and digestive tract tumors in Donryu rats by 1-propyl-1-nitrosourea. 105 69

The leukemogenic effect of 1-propyl- and 1-butyl-1-nitrosourea (PNU and BNU) was studied in Donryu and Sprague-Dawley rats, which received the chemical in their drinking water. BNU produced leukemia in 42 out of 46 (91%) of the Donryu rats, and the majority of the induced leukemia were myeloblastic type. In the Sprague-Dawley rats, the incidence of leukemia was 70% (47/67), of which 37%(13/35) were myelocytic leukemia, although the development of myeloblastic leukemia was still predominant (54%, 19/35). The leukemogenic activity of PNU was slightly lower than that of BNU; it produced leukemia in 64% (61/95) of the Donryu rats. The predominant type of induced leukemia was myelocytic leukemia (59%, 36/61). Therefore, it was demonstrated through the series of experiments using BNU and PNU that the strength of leukemogenic activity has a close relationship to the types of leukemia induced in animals. Both BNU and PNU, however, provide excellent disease models of myelogeneous leukemia in the human being.
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PMID:Leukemias induced by 1-butyl- and 1-propyl-1-nitrosoureas in the rat. 105 41

Three groups of female Donryu rats were given continuously 1-ethyl-1-nitrosourea, 400, 200, or 100 mg/liter, in their drinking water. Leukemias developed in 94 of 104 (92%) rats surviving more than 6 experimental weeks. Of the leukemias, the erythroleukemias were induced most frequently, rapidly, and selectively. Other types of leukemias were found in a few rats of the high-dose group and, in some cases, in rats of the low-dose group. Tumors were also induced in the digestive tract, mammary glands, ear duct, and other organs, but their incidences were lower than 24%.
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PMID:Rapid and selective induction of erythroleukemia in female Donryu rats by continuous oral administration of 1-ethyl-1-nitrosourea. 106 98

The largest excess in tumor incidence due to pollution (616%) was observed in the fish species: Ictalurus nebulosis (the brown bullhead). Extensive analysis of waters on the Fox River in Illinois disclosed a heavy chemical and physical organic and inorganic materials far exceeding State and Federal minimal safety standards. Additional tests showed the presence of numerous human viral agents in the Fox River. Certain chemicals in the water appear to be potential carcinogens for fish. Two types of leukemia were found in 11% of the Esox lucius caught in the Fox River. It is hypothesized that these leukemias might also be of viral etiology. Experiments were conducted on Esox lucius caught in the Fox River. It is hypothesized that these leukemias might also be of viral etiology. Experiments were conducted on Esox lucius (Northern Pike). Interest centered around the possible viral origin of lymphosarcoma of the jaw in that species. Cell-free filtrates of this tumor were inoculated into a test group of fish from pollution-free waters. At the end of seven weeks, lymphosarcoma developed in 89% of the fish inoculated with cell-free homogenates. Control fish receiving inoculation of either Hank's balanced salt solution (HBSS) or normal tissues and kept in separate tanks at all times did not develop lymphosarcomas.
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PMID:Tumors in fish caught in polluted waters: possible explanations. 117 15

We have used the spleen colony assay system and survival duration studies in male DBA/2 mice with P388 leukemia to study the effects of microsomal enzyme induction by phenobarbital on the antileukemic activity and bone marrow toxicity of cyclophosphamide. Phenobarbital drinking water (0.5 mg/ml) was given for 7 days prior to cyclophosphamide (10 to 200 mg/kg i.p.). Average daily phenobarbital intake per mouse was 1.25 mg (equivalent to 4 mg/kg/day human dosage). Dose-response curves with and without phenobarbital pretreatment showed a constant 90% (1-log) reduction in the toxicity of cyclophosphamide to leukemic colony-forming units, whereas enzyme induction had no effect on the toxicity of the drug to normal bone marrow colony-forming units. Parallel survival studies confirmed the 1-log diminution in the antileukemic activity of cyclophosphamide in phenobarbital-pretreated mice. This phenobarbital-induced change in the antitumor activity of cyclophosphamide appears explainable on a pharmacokinetic basis. The Friedman and Boger assay for plasma alkylating metabolites showed that the reduction in the area under the plasma metabolite curve caused by enzyme induction exactly predicted the observed reduction in cyclophosphamide antitumor effect.
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PMID:The effect of phenobarbital on cyclophosphamide antitumor activity. 127 88


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