Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Administration of ACTH to rapidly growing weanling rats results in an increase of DNA synthesis in adrenal and a decrease in liver. Dexamethasone administration decreases both adrenal and liver DNA synthesis. When both hormones were administered to the same animals, the liver DNA synthesis was similar to that observed with dexamethasone alone, but the DNA synthesis in adrenal was lower than that obtained with ACTH alone, yet higher than that observed with dexamethasone. The plasma levels of corticosterone were similar in animals treated with ACTH or with ACTH plus dexamethasone. Aminoglutethimide stimulated adrenal DNA synthesis, but less than ACTH. This substance overcame partially the inhibitory effects of dexamethasone on liver DNA synthesis but did not in adrenal. When both ACTH and aminoglutethimide were given simultaneously, adrenal DNA synthesis was higher than that observed with each substance alone. In all experiments in which adrenal cytosol DNA polymerase was studied, the activity varied in the same direction as DNA synthesis. These results indicate opposing effects of ACTH and glucocorticoids on adrenal DNA synthesis. The finding of a glucocorticoid effect on the adrenal is supported by the demonstration of a glucocorticoid specific binding protein in adrenal cytosol. Cycloheximide blocks the stimulatory action of ACTH on both steroidogenesis and DNA synthesis. Actinomycin D, as well as dexamethasone, blocks only the DNA synthesis-promoting action of ACTH. This latter result suggests some differences in the metabolic pathways by which ACTH controls steroidogenesis and growth in the adrenal cell.
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PMID:Opposite effects of ACTH and glucocorticoids on adrenal DNA synthesis in vivo. 19 Dec 38

Low-dose ionizing radiation caused definite stimulation of immune reactions both in humans and mice. The PFC reaction in response to SRBC immunization and the NK activity of the splenocytes were significantly enhanced after low-dose whole body irradiation. Activation of the T lymphocytes, especially the TH, with increased production of IL-2, might be a critical step in the whole process of immunoenhancement. A single dose of 75 mGy X-rays caused significant lowering of hypothalamic M-Enk content as well as serum corticosterone level. The increased serum testosterone level would exert an inhibitory influence on the CRF-ACTH-CS system to keep the blood corticosterone at a lower than normal level which might facilitate the immune reactions in the SRBC-immunized animals. The increased catecholamines in the spleen would probably reinforce this effect resulting in immunoenhancement. Low-dose ionizing radiation caused increased repair of the genetic material at both the molecular and subcellular levels. The UDS of human and murine lymphocytes was augmented by single or continuous low-dose irradiation. The stimulation of DNA polymerase activity might be responsible for such effects. Exposure to very small doses of low LET radiation could induce in different tissues an adaptive response which alleviated chromosome damage caused by subsequent larger dose radiation. Such an adaptive response could be induced both in vivo and in vitro in different animal species. The induced adaptive response faded away after 3 cell cycles could be re-induced by a second exposure to low-dose radiation. The mechanism of the inductive process needs further study.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Radiation hormesis. A new concept in radiological science. 251 54

Primarily resulting as a spin-off of the search for effective anti-HSV or anti-HIV agents, several compounds have been identified as effective and promising candidate anti-HBV drugs, i.e. famciclovir (penciclovir), BMS-200475, lamivudine (3TC), (-)FTC, L(-)Fd4C, L-FMAU, DAPD (DXG), bis(POM)-PMEA and bis(POC)-PMPA. They all inhibit HBV replication in Hep G2 2.2.15 at concentrations that are well below the cytotoxicity threshold. All these nucleoside analogues require three phosphorylation steps to be active, in their triphosphate form, as inhibitors of the HBV DNA polymerase, except for PMEA (adefovir) and PMPA (tenofovir), which need only two phosphorylation steps, to PMEApp and PMPApp, respectively, to interact as chain terminators with the HBV DNA polymerase reaction. Several of these compounds (for example, famciclovir, lamivudine and adefovir) have proven to be efficacious in the duck and/or woodchuck hepatitis models, and, accordingly, famciclovir, lamivudine and adefovir have also proven to be effective (i.e. in reducing HBV DNA levels) in patients with chronic HBV infection. Yet, famciclovir and lamivudine may lead to the emergence of resistance mutations (i.e. L528M and M552V/I) in the HBV DNA polymerase upon long-term treatment. These penciclovir- and lamivudine-resistant HBV mutants still retain susceptibility to adefovir, which, in turn, has so far not been found to engender resistance mutations in HBV. As has become obvious from the experience with the treatment of HIV infections, future HBV chemotherapy may reside in combination drug therapy so as to achieve the highest possible virus reduction, thereby minimizing the likelihood of drug resistance development.
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PMID:Perspectives for the treatment of hepatitis B virus infections. 1041 52