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)

1 A simple, specific assay for 6-mercaptopurine (6-MP) in human plasma with a sensitivity of 10 ng/ml (66 nmol/1) has been developed. 2 6-MP was extracted directly from plasma into toluene using a novel extraction procedure. This involves conversion of 6-MP into a phenyl mercury derivative by its reaction with phenyl mercuric acetate in alkaline plasma and extracting into toluene. Back-extraction of the toluene layer with 0.1N HCl regenerates 6-MP, which is then oxidised to purine-6-sulphonate and assayed fluorimetrically. 3 This assay has been modified to measure azathioprine and a new thiopurine metabolite in plasma. 4 In a kidney transplant patient given azathioprine, 50 mg i.v., conversion to 6-MP was rapid and the plasma half-life of 6-MP was 36 min. 5 These assays are suitable for studying the pharmacokinetics of azathioprine in patients with kidney transplants. The 6-MP assay should also prove useful for studying the pharmacokinetics of the drug in patients with leukaemia.
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PMID:Assay of azathioprine, 6-mercaptopurine and a novel thiopurine metabolite in human plasma. 4 May 85

In view of the marked antitumor activity of 3-deazauridine, the synthesis of 4-(beta-D-ribofuranosyl)-1,3-dihydroxybenzene (1,3-dideazauridine) and its dibenzyl derivative was carried out. 4-Bromo-1,3-dihydroxybenzene was converted to its dibenzyl derivative, which, upon reaction with n-butyllithium followed by treatment with anhydrous cadmium chloride, gave bis(1,3-dibenzyloxyphenyl-4)cadmium. Condensation of this intermediate with 2,3,5-tri-O-benzoyl-D-ribofuranosyl chloride in refluxing toluene, and subsequent removal of the protecting benzoyl groups, afforded 4-(beta-D-ribofuranosyl)-1,3-dibenzyloxybenzene which, upon catalytic hydrogenation over Pd/C, furnished the desired 4-(beta-D-ribofuranosyl)-1,3-dihydroxybenzene. The beta configuration at the anomeric center was established by NMR and hydrogen bonding studies. 4-(Beta-D-ribofuranosyl)-1,3-dibenzyloxybenzene inhibited the growth of leukemia L1210 cells by 50% at 7 x 10(-6) M, and that of mammary carcinoma TA3 cells at 5 x 10(-5) M. Dideazauridine itself was less active, inhibiting the leukemia L1210 but not the TA3 cells at 1 x 10(-4) M, but the compound was significantly active against herpes simplex (type I) virus in vitro.
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PMID:Synthesis and biological activity of 4-beta-Iribofuranosyl-1,3-dihydroxybenzene ("1,3-dideazauridine"). 16 82

A convenient synthesis of 8-azapurine ribonucleosides substituted at the 6 position with thio, alkylthio, alkoxy, amino, and alkylamino groups is described. The reaction of 6-(methylthio)-8-azapurine (1) with 2,3,5-tri-O-acetyl-D-ribofuranosyl chloride in the presence of Linde AW-500 molecular sieve gave a 2:1 mixture of 2 and 3, respectively. This mixture was rearranged by heating with molecular sieve in refluxing toluene to give a 6:1 mixture of 2 and 3. Treatment of 2 or 3 with the appropriate nucleophiles at room temperature gave 6-substituted 8-azapurine ribonucleosides (7-substituted 2- or 3-beta-D-ribofuranosyl-3H-1,2,3-triazolo[4,5-d]pyrimidines) 4-13. The thione 11 rearranges to N-beta-D-ribofuranosyl[1,2,3]thiadiazolo[5,4-d]pyrimidin-7-amine (14) in the solid state or in solution. All of these compounds were cytotoxic to H.Ep. No. 2 cells in culture except the parent base, 8-aza-6-(methylthio)purine (1) and the 8-isomers (3,12, and 13). Three of these compounds-8azaadenosine (4), 8-aza-6-(methylthio)purine ribonucleoside (5), and 8-aza-6-(methoxy)purine ribonucleoside (7)-showed borderline activity in the leukemia L1210 system. The thiadiazolopyrimidine (14) showed activity at three dose levels.
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PMID:Analogues of 8-azainosine. 55 73

Studies in humans and animals have shown that gasoline contains a number of cancer-causing and toxic chemicals such as 1,3-butadiene, benzene, toluene, ethylbenzene, xylenes, isoparaffins, methyltert-butylether, and others. The International Agency for Research on Cancer (IARC) in its Monograph Supplement 7 (1987) concludes that "in the absence of adequate data on humans, it is biologically plausible and prudent to regard agents for which there is sufficient evidence of carcinogenicity in experimental animals as if they present a carcinogenic risk to humans." Epidemiological studies in humans provide important evidence of potential increased risk of leukemia, lymphatic tissue cancers, cancers of the brain, liver, and other organs and tissues. Recently (July, 1990) the American Conference of Governmental Industrial Hygiene (ACGIH) recommended that the TLV-TWA for benzene be reduced from 1 ppm to 0.1 ppm (ACGIH, 1990). The Collegium Ramazzini and others have also recommended that the exposure level for 1,3-Butadiene be reduced from 1,000 ppm to below 0.2 ppm. This recommendation is based on the findings that were presented at the Symposium on Toxicology, Carcinogenesis, and Human Health Aspects of 1,3-Butadiene (Environ. Health Perspec., 1990). Thus, studies on health effects resulting from very low levels of benzene, 1,3-butadiene, and other cancer-causing chemicals--components of gasoline--necessitate that all avoidable exposure to gasoline or gasoline vapors be avoided.
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PMID:Dangerous and cancer-causing properties of products and chemicals in the oil refining and petrochemical industry: Part I. Carcinogenicity of motor fuels: gasoline. 178 Aug 52

We have examined the cis-acting RNA packaging signal (psi) from Moloney murine leukemia virus using a combination of chemical and primary sequence analysis techniques. For our chemical analyses, we used dimethyl sulfate, kethoxal, and 1-cyclohexyl-3-(2-morpholinoethyl)-carbodiimide metho-p-toluene sulfonate as probes for RNA secondary structure. The structural information obtained from these studies was used to constrain computer algorithms for prediction of RNA secondary structure. In addition, we generated and analyzed a phylogenetic comparison of homologous sequences from related retroviruses. From these data, we have developed two models for the RNA secondary structure of the packaging signal psi. Both of these models suggest the presence of secondary structure elements in a region of the psi RNA known to be required for function.
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PMID:RNA secondary structure analysis of the packaging signal for Moloney murine leukemia virus. 185 63

Gasoline contains large numbers of dangerous and cancer-causing chemicals such as benzene, butadiene, toluene, ethylbenzene, xylene, trimethyl pentane, methyltertbutylether (MTBE) and many others. For the U.S. alone approximately 140 billion gallons of gasoline were consumed in 1989. An increase in only ten cents per gallon in price of gasoline generates 14 billion dollars in extra profit per year for oil industry cartel. Laboratory animals exposed to gasoline developed cancers in different tissues and organs. A number of epidemiological studies in humans provide evidence of increased cancer risk of leukemia, kidney, liver, brain, lymphosarcoma, lymphatic tissue pancreas and other tissues and organs.
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PMID:Dangerous properties of petroleum-refining products: carcinogenicity of motor fuels (gasoline). 168 9

Benzene. The evidence for carcinogenicity of benzene in humans was evaluated by the IARC in 1982 as follows: "It is established that human exposure to commercial benzene or benzene-containing mixtures can cause damage to the haematopoietic system, including pancytopenia. The relationship between benzene exposure and the development of acute myelogenous leukaemia has been established in epidemiological studies. "Reports linking exposure to benzene with other malignancies were considered to be inadequate for evaluation. "There is sufficient evidence that benzene is carcinogenic to man." This evaluation now warrants some elaboration and updating. While the epidemiological evidence concerning benzene carcinogenicity is strongest for acute myelocytic leukaemia, there is some limited evidence of increased risks of chronic myeloid and chronic lymphocytic leukaemia. In addition, recent studies have suggested an increased risk of multiple myeloma, while others indicate a dose-related increase for total lymphatic and haematopoietic neoplasms. Corroborative evidence for such a generalized effect comes from experimental studies showing that exposure to benzene depresses all lympho-haematopoietic cell lines. While only limited evidence of benzene carcinogenicity in experimental animals exists, the recent findings of the National Toxicology Program (NTP, 1984) in the U.S.A. and Maltoni et al. (1985) strongly indicate that benzene is an experimental carcinogen. Toluene and xylene. While no direct human evidence is available, there is recent evidence of carcinogenicity of toluene and xylene at high concentrations in experimental animals. It should also be noted that any future epidemiological observations of cancer risks associated with toluene or xylene would have to take account of the suspected effects of benzene impurities.
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PMID:Carcinogenicity of benzene, toluene and xylene: epidemiological and experimental evidence. 305 47

A suspicion of an excess cancer risk in automotive model shops prompted the Industrywide Studies Branch, NIOSH, to conduct a proportionate mortality study and an industrial hygiene characterization of operations in these shops. The mortality study showed a statistically significant excess proportion of deaths due to colon cancer and leukemia (for woodshops only). The materials used in the model shops include various natural woods, laminated woods, plastics, resins, varnishes, putties and paints. Personal breathing zone samples were collected for total and respirable dust, amines, various hydrocarbons (including styrene, and toluene), formaldehyde, and nitrosamines. Particle size distribution studies were conducted on the wood dust and bulk airborne samples of dusts were subjected to various mutagenicity test systems. Work practices, ventilation and general housekeeping were checked. Total wood dust samples ranged from 0.03 to 25 mg/m3 with an average around 1.0 mg/m3. The percent respirable dust ranged from 19 to 38% as measured with Andersen impactors. Solvent exposure samples ranged from non-detectable to about 10% of the OSHA Permissible Exposure Levels. Relevant recommendations for improvement of contaminant control were made.
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PMID:Industrial hygiene characterization of automotive wood model shops. 388 Jan 87

Short-term exposure to certain solvents, such as several halogenated hydrocarbons, petroleum distillates, ethylene glycol, ethylene glycol ethers, and diethylene glycol, may cause renal tubular necrosis. Tubular lesions with metabolic acidosis have been reported in addicts inhaling solvent vapor (eg, toluene). A Goodpasture's syndrome may be induced by acute or subacute exposure to solvents, but its incidence is rare. No adequate proof is yet available that repeated exposure to nonsubstituted organic solvents may lead to the development of different types of chronic glomerulonephritis, but the available epidemiologic data are suggestive of the existence of such an association. Only a few solvents have been reported to act on the hematopoietic system of humans. The hematotoxicity (aplastic anemia, leukemia) of benzene is well established. Some ethylene glycol ethers are also toxic to bone marrow.
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PMID:Kidney disorders and hematotoxicity from organic solvent exposure. 390 73

A previous epidemiologic study of the U.S. rubber industry indicated that there has been an excess of leukemia and lymphoma mortality among hourly workers at one styrene-butadiene rubber manufacturing plant. This investigation was a combined industrial hygiene and hematology cross-sectional survey at the same plant. The objectives of the survey were to quantify exposure levels for styrene, butadiene, benzene and toluene, and to relate these levels to hematologic variation. Personal air samples and blood specimens were obtained from 157 production workers. All exposure levels for the four chemicals assayed were well below recommended standards. The higher mean styrene (13.67 ppm) and butadiene (20.03 ppm) concentrations were found in the Tank Farm area; in all other departments the mean levels for the four chemicals were less than 2 ppm. The Tank Farm workers had slightly lower levels of circulating erythrocytes, hemoglobin, platelets and neutrophils, and slightly higher mean corpuscular red cell volumes and neutrophil band counts than the other workers. Overall, in this population there was no pronounced evidence of hematologic abnormality, as determined from examination of peripheral blood.
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PMID:A hematology survey of workers at a styrene-butadiene synthetic rubber manufacturing plant. 706 11


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