Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.44 (AGT)
 770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The kinetics of accumulation of the premutagenic DNA adduct O6-methylguanine (O6-meG) in the liver, blood leukocytes, lymph nodes and bone marrow of rats was examined and compared after single or multiple doses of procarbazine, a methylating cytostatic drug employed in the treatment of Hodgkin's lymphoma patients, and methylnitrosourea (MNU), an experimental methylating agent and carcinogen. Maximal O6-meG levels occurred 1-2 h after administration of single doses of procarbazine (10 mg/kg) or MNU (1 mg/kg), thereafter decreasing with half-lives of approximately 20-45 h, depending on the tissue. A relatively uniform tissue distribution was observed with both agents, with the liver generally showing highest adduct levels, followed by the lymph nodes, bone marrow and blood leukocytes which contained broadly similar amounts of O6-meG. During daily, oral administration to rats of procarbazine for 10 days at dose rates of 2.5, 5, 10 or 20 mg/kg/day (treatment analogous to that of the MOOP chemotherapy protocol for Hodgkin's lymphoma) followed by animal death on different days (in each case 24 h after the last treatment), a biphasic mode of O6-meG induction was observed: an initially steep build-up during the first 3-4 days was followed by a transient decline in the rate of accumulation, in turn followed by a second wave of accumulation and then a further slow-down. During the same treatment, liver O6-methylguanine-DNA alkyltransferase (AGT) declined in a dose-related manner. AGT recovery after the end of treatment was slow, taking nearly 20 days after the end of the high-dose treatment to return to control levels, despite the fact that all detectable adducts had been lost from DNA within 3 days after the end of treatment. A similar depletion and slow recovery of AGT in the liver, blood lymphocytes, bone marrow and lymph nodes was observed after treatment with a single dose of 100 mg/kg procarbazine. In contrast to these observations, O6-meG accumulated smoothly during a 10 day administration of MNU (1 or 10 mg/kg/day) to reach a steady-state within 5-6 days, while liver AGT was partially depleted after the high dose and recovered fully within 72 h of cessation of treatment. Similarly, a single dose of MNU (35 mg/kg) resulted in AGT depletion followed by rapid recovery in all four tissues examined. It is concluded that procarbazine (but not MNU) causes a decrease in cellular AGT concentrations by a mechanism additional to suicide repair of O6-meG.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Differential effects of procarbazine and methylnitrosourea on the accumulation of O6-methylguanine and the depletion and recovery of O6-alkylguanine-DNA alkyltransferase in rat tissues. 751 72

Objective: Extranodal natural killer /T-cell lymphoma (ENKTL) is an aggressive and unusual subtype of non-Hodgkin lymphoma (NHL) that it is related with the Epstein-Barr virus (EBV). CSF is considered as an ideal source of high-concenrtation disease-related proteins. We aimed at identifying the proteomic markers changes of CSF in ENKTL patients and used such changes to diagnose ENKTL. Materials and methods: In this study, CSF samples were acquired from hospitalization patients from the Cancer Center of West China Hospital, Chengdu, China. Comparative proteomic profiling are commonly used to do label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS). And in this study the same method was used to characterize the variety of proteins in ENKTL patients and none-ENKTL people. Results: In the aggregate, 421 non-excrescent and functional proteins were identified among the samples. Of these proteins, 45 proteins quantified match the involved criteria. HRG, TIMP-1, SERPINA3, FGA, FGG, TF, FGB, APP, and AGT were significantly up-regulated. Discussion: We discovered that some proteins were significantly up-regulated. Also, these proteins themselves or with others proteins may be potential markers to diagnose ENKTL. The changes of proteomics may be a potential method to precisely identify the pathogenesis of the ENKTL.
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PMID:Proteomic Analysis of Cerebrospinal Fluid From Patients With Extranodal NK-/T-Cell Lymphoma of Nasal-Type With Ethmoidal Sinus Metastasis. 3199 45