Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An HL-60 in vitro transcription assay was developed and used to monitor HL-60 human promyelocytic leukemia cell transcription during calcitriol-induced monocytic differentiation. Treatment of cells with calcitriol (50 nM) for 96 h produced a 48% reduction in total DNA-dependent RNA polymerase activity with a corresponding reduction in alpha-amanitin-sensitive (RNA polymerase II) activity. Nuclei isolated from cells treated with the less efficacious vitamin D analogues, 24,25-dihydroxyvitamin D3, and 1 alpha-hydroxyvitamin D3, did not exhibit nuclear transcription that was significantly different from control nuclei. Transcription in nuclei isolated from calcitriol-treated cells was decreased by 40 to 50% concomitant with monocytic differentiation, as assayed by acquisition of nitroblue tetrazolium reducing activity. Maximal decrease in transcription was achieved by 45 h postinduction, whereas expression of nitroblue tetrazolium reducing activity peaked at approximately 70 h, and decreased DNA synthesis was evident by 48 h. These observations suggest that calcitriol induction of HL-60 differentiation results in monocytes with reduced requirements for gene transcription and that transcription changes accompany expression of nitroblue tetrazolium reducing activity.
Cancer Res 1986 Oct
PMID:Effects of calcitriol on nuclear transcription during human HL-60 promyelocytic leukemia cell differentiation. 346 8

Several mechanisms are proposed for explaining the antitumor activity and the toxicity of anthracyclines. The first recognized biochemical target is DNA. Anthracyclines and DNA lead to the formation of complexes of intercalation. The intercalation can explain biochemical properties such as inhibition of DNA polymerase and of RNA polymerase. On the other hand, the intercalation cannot explain the chromosomal damages observed in cancer cells following in vivo administration or in vitro incubation. Additional mechanisms are proposed such as biological reduction of quinone C ring, leading to the formation of radical species able to react covalently with DNA. More recently, an interaction of anthracyclines with topoisomerase II has been also described. There is no clear correlation between antitumour efficacy and DNA intercalation. However it must be pointed out that no anthracycline has been found so far which shows antitumour activity dissociated from the ability of interacting with DNA. Anthracyclines interact with membranes: interaction with negatively charged phospholipids like cardiolipin; peroxidation of membrane lipids following biological reduction of the quinone C ring. These membrane effects are believed to be responsible for chronic cardiac toxicity. The clinical activity of daunorubicin and of doxorubicin leads to considerable work with the hope to discover more active and/or less toxic congeners. Several possibilities are investigated: isolation of new anthracyclines from natural sources (fermentation broths); chemical modifications of the whole molecule; total synthesis of new sugars and of new aglycones.
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PMID:[Structure and activity of anthracyclines]. 355 Jun 4

Single intraperitoneal administration of benzo[a]pyrene (B[a]P) at 20 mg/kg body weight to male Wistar rats caused an early (2 h) inhibition in liver of gross transcription as measured by incorporation of [14C] orotic acid into nuclear RNA. This inhibition was reversed gradually into a partial stimulation at 2-4 days after administration of B[a]P, followed by another period of inhibition at 7 days which persisted up to 14 days. The early reversible inhibition at 2 h was probed further by studies on in vitro transcription using isolated nuclei from treated rats. It was observed that total expression of RNA polymerase activity was only marginally inhibited because, while expression of RNA polymerases II and III showed remarkable inhibition, RNA polymerase I showed stimulation in activity.
Cancer Lett 1987 May
PMID:Modulation of transcription in rat liver by benzo[a]pyrene. 358 Oct 49

Retinoids are effective inhibitors of chemical carcinogenesis in the skin, mammary gland, esophagus, respiratory tract, pancreas, and urinary bladder of experimental animals. Modification of the basic retinoid structure has produced retinoids with enhanced target organ specificity, resulting in increased anticancer activity with reduced systemic toxicity. Newer retinoidal benzoic acid derivatives are even more active. Combining retinoid treatment with other modulators of carcinogenesis results in a synergistic inhibition of tumor development. Retinoids in combination with hormonal manipulation are much more effective in inhibiting mammary carcinogenesis than is either treatment alone; this combination approach also inhibits mammary tumor recurrence following surgical removal of the first tumor. Retinoids are most effective when administered shortly after the carcinogenic insult. However, even when retinoid treatment is delayed, the compounds are still effective cancer chemopreventive agents for the mammary gland and urinary bladder. The time that retinoid exposure can be delayed and retain an anticancer effect is directly related to tumor latency, with a longer delay permissible against tumors with long latent periods. The mechanism(s) by which retinoids inhibit carcinogenesis is unknown; however, in the mammary gland, retinoids inhibit differentiation and proliferation, DNA synthesis, and RNA polymerase activity. Cytosolic retinoid-retinoid receptor complexing is apparently a prerequisite for the nuclear interaction of retinoids, at least in mammary cells.
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PMID:Anticarcinogenic effects of retinoids in animals. 359 31

The effects of dietary phenobarbital (PB) on RNA polymerase II (nucleoside triphosphate: RNA nucleotidyltransferase, EC 2. 7. 7. 6) in the liver of male Sprague-Dawley rats previously administered diethylnitrosamine (DENA) were studied. When a diet containing 0.05% phenobarbital was administered, the activity of DNA-dependent RNA polymerase II in the liver nuclei of rats was temporarily increased 1 and 2 weeks after the onset of feeding and expressed to be relatively higher afterwards, compared with the activity in rats fed the control diets.
Cancer Lett 1985 Mar
PMID:Effect of phenobarbital on the activity of RNA polymerase II during diethylnitrosamine-induced hepatocarcinogenesis in the rat. 397 8

The growth of MCF-7 cells was arrested by 24 h of isoleucine deprivation. Following replenishment of the medium, the incorporation of uridine and thymidine into trichloroacetic acid-precipitable material began to increase slowly and gradually rose to the level of cycling cells. The addition of 5 X 10(-9) M estradiol to growth-arrested cells dramatically shortened the time of onset of macromolecular synthesis and increased the overall amount of precursor incorporation 2- to 4-fold over the level obtained by arrested control cells. The increase in uridine incorporation preceded the increase in thymidine incorporation by 6 h. Inhibition of protein synthesis with cycloheximide blocked the recovery of macromolecular synthesis in both control and estrogen-treated cells. Actinomycin D was ineffective in blocking the estrogen-stimulated recovery of macromolecular synthesis at concentrations known to inhibit pre-rRNA synthesis (10(-8) M). At higher concentrations, uridine and thymidine incorporation were inhibited in a dose-dependent manner. Inhibition of RNA polymerase II activity with alpha-amanitin similarly blocked both the recovery of the cells from isoleucine starvation and the potentiation of this by estradiol. Dihydrofolate reductase and thymidine kinase activities are both stimulated by estradiol in MCF-7 cells. In cycling cells, estrogen stimulates a 2-fold increase in their messenger RNAs (mRNAs) within 24 h. The level of dihydrofolate reductase mRNA is unaffected by isoleucine starvation, and estrogen caused no change in dihydrofolate reductase mRNA levels over a 24-h period following reversal of growth arrest. Similar results were observed for the 600-nucleotide pS2 mRNA that has been identified as an estrogen-induced RNA in MCF-7 cells. In contrast, thymidine kinase mRNA was found to be increased by estrogen at 24 h, but not at 12 h, following reversal of growth arrest. This increase correlates with increases in thymidine, but not uridine incorporation. These data indicate that the estrogen-stimulated increase in thymidine incorporation following release from growth arrest is dependent on new RNA synthesis. However, the hormone did not increase the levels of three estrogen-regulated mRNAs coordinately with the increases observed in uridine incorporation.
Cancer Res 1985 Jun
PMID:Relationship between the expression of estrogen-regulated genes and estrogen-stimulated proliferation of MCF-7 mammary tumor cells. 398 99

The availability of a purified RNA-instructed DNA polymerase (reverse transcriptase) from avain myeloblastosis virus provided the opportunity to explore whether this enzyme could be used as a general tool for synthesizing DNA complements of a wide variety of natural RNAs. The results described show that this potentially useful situation is in fact realized. The avian viral transcriptase can mediate the synthesis of DNA complementary to RNAs of such widely divergent origins as Qbeta bacteriophage and Moloney sarcoma virus. These findings open up novel pathways for the experimental resolution of several interesting problems. Thus, given a purified RNA message, one should be able to synthesize the corresponding DNA genetic material. If suitably labeled, the synthetic DNA has various obvious uses, including its use via molecular hybridization as an analytical probe for the corresponding gene on the chromosomes or for its message in a complex mixture of RNA molecules. Of immediate practical interest is the import of these findings for viral oncology. They imply that for many purposes we will not be compelled to isolate or use the "reverse transcriptase" from each oncogenic virus in order to synthesize its complementary DNA. The ability of one enzyme to accept a variety of oncogenic RNAs will obviate many of the logistical difficulties that arise, particularly in attempts to illuminate the etiology of human cancer.
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PMID:Synthesis of DNA complements of natural RNAs: a general approach. 433 Sep 45

The activity of RNA polymerase has been determined in the nuclear fraction of normal mouse ovaries, 60-day-old preneoplastic intrasplenic ovarian grafts, and ovarian tumours developed after 7 months of ovary grafting into the spleen. In preneoplastic grafts, RNA polymerase activity corresponds to that of normal ovaries, while in ovarian tumours, the enzyme value was 2-3 times higher. Oestradiol injected for 10 days, acting as depressant of the host pituitary gonadotrophic potency, decreased the enzyme level in the grafts, whereas no change was observed in similarly treated tumours. These facts indicate that hormonal mechanisms regulating the genetic nuclear expression are operating only in the 2-month-old preneoplastic ovarian cell, while autonomy from these regulating mechanisms is achieved by 7-month-old tumour cells.
Br J Cancer 1971 Mar
PMID:Differential response of ribonucleic acid polymerase in preneoplastic and neoplastic ovaries of mice following oestradiol treatment. 508 11

Peripheral blood lymphocytes of domestic cats were co-cultivated with lethally irradiated MT-2 cells, which produced human T-cell leukemia virus type 1 (HTLV-I). Two cat lymphoid cell lines, CaL-1 and CaL-2, established and maintained without exogenously added T-cell growth factor, were characterized after more than 6 months of cultivation. These cells grew in suspension, had a chromosome number of 38 and lacked cytoplasmic and surface immunoglobulins. CaL-2 cells formed E-rosettes. Both cell lines harbored HTLV genomes but not human Alu family sequences, which are highly repetitious in the human genome, suggesting that transfer of human DNA fragments was not necessary for their immortalization or transformation. HTLV antigens were detected in CaL-1 and CaL-2 cells by indirect immunofluorescence assay. CaL-1 and CaL-2 cells both expressed viral proteins with apparent molecular weights of 53 kd, 24 kd and 19 kd, and CaL-2 cells also expressed 28 kd and 20 kd proteins. Reverse transcriptase activity was detected in culture fluid of CaL-2 cells, but not of CaL-1 cells. CaL-2 cells but not CaL-1 cells had syncytium-induced activity. These findings indicated that lymphocytes of cats, especially T lymphocytes, were susceptible to infection with HTLV and to immortalization by HTLV.
Int J Cancer 1984 Oct 15
PMID:Immortalization of peripheral blood lymphocytes of cats by human T-cell leukemia virus. 609 83

The present study describes the separation and purification of a reverse transciptiase from an orbital tumor of a patient with acute myelomonocytic leukemia. Specific reaction conditions with respect to ionic requirements and template-primers are reported. The purified enzyme was able to transcribe (rA)n . (dT)12, (rC)n . (dG)12, (OMeC)n . (dg)12 and the 70 S RNA from R(Mu)LV. Serological studies that the reverase transcriptase is antigenically related to reverse transcriptase from the type C woolly monkey virus-gibbon ape leukemia virus group.
Cancer Lett 1980 Mar
PMID:RNA-dependent DNA polymerase activity in ocular granulocytic sarcoma associated to acute myelomonocytic leukemia in Turkish children. Biochemical and immunological characterization of the enzyme. 615 28


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