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)

Commercial-grade aurintricarboxylic acid (ATA) inhibits poly(A), poly(C) and viral RNA-directed DNA synthesis by detergent-disrupted virions of Moloney murine leukemia virus. Paper chromatography of crude ATA yields two active components, which appear to behave identically, and at least two inactive components. The concentration of ATA needed to inhibit polymerase activity is proportional to the concentration of viral protein. The inhibition is neither attributable to contaminating heavy metal ions in the ATA preparation nor to chelation by ATA of Mn2+ or Zn2+, the necessary co-factors. Inhibition of the polymerase reaction by ATA greatly increases the Km for the primer [oligo(T)/oligo(dG)], while it only slightly lowers the Vmax and does not affect the Km's for the template [poly(A)/poly(C)] or the substrate (TTP/dGTP). Thus, ATA seems to reduce specifically the affinity of the polymerase for the DNA primer molecule.
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PMID:Inhibition of RNA-directed DNA polymerase by aurintricarboxylic acid. 5 43

Zinc is essential for the growth of all species. Growth arrest results from its deficiency and presumably reflects important roles for this metal at critical points of metabolism. Studies of zinc metalloenzymes show that zinc serves as a coenzyme to more than 80 enzymes, among which are the reverse transcriptases which cause leukemia in many species. Its role in nucleic acid metabolism is emphasized.
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PMID:Zinc biochemistry in normal and neoplastic growth processes. 6 66

omicron-Phenanthroline, a zinc chelating agent, is known to inhibit the DNA polymerase activity of cellular DNA-dependent and viral RNA-dependent DNA polymerases. We find that omicron-phenanthroline does not inhibit the reverse transcriptase-associated RNase H activity of retroviruses. Kinetic studies, using DNA template-primers as an inhibitor of RNase H, suggest that zinc does not play any role in template-primer binding by reverse transcriptase. These results also indicate a distinct binding site for the template and triphosphate substrates. Cellular RNase H from calf thymus and RNase H-II from Rauscher leukemia virus are likewise resistant to omicron-phenanthroline inhibition, implying non-involvement of zinc in the nucleic acid hydrolysis by these enzymes.
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PMID:Reverse transcriptase-associated ribonuclease H does not require zinc for catalysis. 8 44

Analogues of cis-dichlorodiammineplatinum(II) were prepared in which substituted pyridines (A), 1-(4-aminobenzylidene)indene (B), or DL-3,5,3'5'-tetraoxo-1,2-dipiperazinopropane (ICRF-159) was used in place of ammonia, and in some cases platinum(IV) or palladium(II) was used in place of the platinum(II). Both platinum complexes with ICRF-159 were active against leukemia 1210, but none of the others produced significant life extension following a single ip dose of 400 mg/kg. Attempts to prepare complexes of ICRF-159 with Zn(II), Mn(II), and Cr(III) were unsuccessful, but there were indications of complex formation with CuCl2 and with NiCl2.
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PMID:Platinum and palladium derivatives for chemotherapy studies. 45 9

Because zinc is an essential nutrient for tissue growth, cellular division, protein synthesis, and DNA and RNA replication, it also ought to play a critical role in the growth of tumors. To test this thesis, a series of experiments were performed to test the effect of zinc deficiency on the lethality of a variety of solid and ascites tumors in mice and rats. Specifically, the following models were tested: Walker 256 carcinosarcomas, solid and ascites forms in rats; three mouse leukemias (L5178yf, L1210, and P388) in CDF, male mice; and Lewis lung carcinoma in C57BI/6 male mice. Rats receiving a zinc-deficient diet showed marked reduction of tumor growth, both of solid or ascites models, and this was accompanied by striking increase in survival. Survival of mice with transplanted leukemia was also significantly prolonged by zinc deficiency. In addition, growth of the Lewis lung carcinoma was inhibited, but the survival through increased, was probably limited by the adverse effects of zinc deficiency. The results suggest that tumor inhibition is a general effect of zinc deficiency, irrespective of cell type, cell growth rate, species, or site of growth. There are numerous potential applications of zinc metabolism to the diagnosis, therapy, and understanding of cancer.
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PMID:Implications of the inhibition of animal tumors by dietary zinc deficiency. 60 51

The per-capita intakes of zinc, cadmium, copper and of chromium were estimated from food consumption data in 28 countries and were found to correlate directly with the age-corrected mortalities from cancers of intestine, prostate, breast, leukemia, skin and of other organs, suggesting that the anticarcinogenic effect of selenium is counteracted by other trace elements. Similarly calculated dietary intakes of manganese are inversely correlated, particularly with the mortalities from cancer of pancreas, an organ normally known to contain high concentrations of this element. Arsenic intakes correlate inversely with the male lung cancer mortalities. A number of other direct and inverse associations were observed which suggest that trace elements in the human diet may hav both benign and adverse effects on tumor development. The zinc concentrations in whole blood collected from healthy donors in the U.S. correlate directly with regional mortalities from cancers of intestine, breast and of other sites. The origin of these associations is discussed primarily in terms of the seleium-antagonistic effect of zinc and of some of the other elements considered. Results of animal experiments and of other studies are cited which support hypotheses that link human cancer development to possible deficiencies or excesses in the dietary trace element intakes.
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PMID:Cancer mortality correlation studies--IV: associations with dietary intakes and blood levels of certain trace elements, notably Se-antagonists. 85 92

Aqueous zinc acetate injected ip prevented tumor growth in 50-70% of BDF male mice previously inoculated ip with L1210 leukemia cells. However, aqueous zinc acetate injected sc did not prevent tumor growth in AKR/J mice inoculated im with BW5147 lymphatic leukemia cells. In the latter mice, only a small but statistically significant increase in mean survival was noted.
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PMID:Effect of zinc administration on the growth of L1210 and BW5147 tumors in mice. 100 17

2-Formyl-3-hydroxy-4,5-bis(hydroxymethyl)pyridine thiosemicarbazone was synthesized in an attempt to direct the chelating potential of this agent to the active site of the zinc-requiring enzyme pyridoxal phosphokinase. Evaluation of the antineoplastic activity of this agent in the sarcoma 180 and L-1210 leukemia systems in mice showed potent activity. The presence or absence of pyridoxine hydrochloride in the diet did not influence the degree of inhibition of the growth of sarcoma 180 ascites cells. In addition, 2-formyl-3-hydroxy-4,5-bis(hydroxymethyl)pyridine thiosemicarbazone was inactive against a subline of sarcoma 180 resistant to 1-formylisoquinoline thiosemicarbazone, suggesting that the former agent may have a biochemical mechanism of action similar to that of the latter. In keeping with this expectation, 2-formyl-3-hydroxy-4,5-bis(hydroxymethyl)pyridine thiosemicarbazone inhibited the synthesis of DNA but not of RNA or protein in sarcoma 180 ascites cells in vitro.
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PMID:Synthesis of site-directed chelating agents II: 2-formyl-3-hydroxy-4,5-bis (hydroxymethyl)pyridine thiosemicarbazone. 125 68

The long terminal repeat of Moloney murine leukemia virus (MuLV) contains the upstream conserved region (UCR). The UCR core sequence, CGCCATTTT, binds a ubiquitous nuclear factor and mediates negative regulation of MuLV promoter activity. We have isolated murine cDNA clones encoding a protein, referred to as UCRBP, that binds specifically to the UCR core sequence. Gel mobility shift assays demonstrate that the UCRBP fusion protein expressed in bacteria binds the UCR core with specificity identical to that of the UCR-binding factor in the nucleus of murine and human cells. Analysis of full-length UCRBP cDNA reveals that it has a putative zinc finger domain composed of four C2H2 zinc fingers of the GLI subgroup and an N-terminal region containing alternating charges, including a stretch of 12 histidine residues. The 2.4-kb UCRBP message is expressed in all cell lines examined (teratocarcinoma, B- and T-cell, macrophage, fibroblast, and myocyte), consistent with the ubiquitous expression of the UCR-binding factor. Transient transfection of an expressible UCRBP cDNA into fibroblasts results in down-regulation of MuLV promoter activity, in agreement with previous functional analysis of the UCR. Recently three groups have independently isolated human and mouse UCRBP. These studies show that UCRBP binds to various target motifs that are distinct from the UCR motif: the adeno-associated virus P5 promoter and elements in the immunoglobulin light- and heavy-chain genes, as well as elements in ribosomal protein genes. These results indicate that UCRBP has unusually diverse DNA-binding specificity and as such is likely to regulate expression of many different genes.
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PMID:Cloning of a negative transcription factor that binds to the upstream conserved region of Moloney murine leukemia virus. 130 93

The effect of chronic dietary zinc deficiency on the carcinogenic potential of dietary cadmium was assessed in male Wistar (WF/NCr) rats. Groups (n = 28) of rats were fed diets adequate (60 ppm) or marginally deficient (7 ppm) in zinc and containing cadmium at various levels (0, 25, 50, 100, or 200 ppm). Lesions were assessed over the following 77 weeks. Zinc deficiency alone had no effect on survival, growth, or food consumption. Cadmium treatment did not reduce survival or food consumption and only at the highest doses of cadmium (100 and 200 ppm) was body weight reduced (maximum 17%). The incidence of prostatic proliferative lesions, both hyperplasias and adenomas, was increased over that seen in controls (1.8%) in both zinc-adequate (20%) and zinc-deficient rats (14%) fed 50 ppm cadmium. The overall incidence for prostatic lesions for all cadmium treatment groups was, however, much lower in zinc-deficient rats, possibly because of a marked increase in prostatic atrophy that was associated with reduced zinc intake. Cadmium treatment resulted in an elevated leukemia incidence (maximum 4.8-fold over control) in both zinc-adequate and zinc-deficient groups, although zinc deficiency reduced the potency of cadmium in this respect. Testicular tumors were significantly elevated only in rats receiving 200 ppm cadmium and diets adequate in zinc. Both zinc-deficient and zinc-adequate groups showed significant positive trends for development of testicular neoplasia with increasing cadmium dosage. Thus, oral cadmium exposure is clearly associated with tumors of the prostate, testes, and hematopoietic system in rats, while dietary zinc deficiency has complex, apparently inhibitory, effects on cadmium carcinogenesis by this route.
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PMID:Carcinogenicity of oral cadmium in the male Wistar (WF/NCr) rat: effect of chronic dietary zinc deficiency. 142 9


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