methylnitronitrosoguanidine and benzamide

methylnitronitrosoguanidine has been researched along with benzamide* in 12 studies

Reviews

1 review(s) available for methylnitronitrosoguanidine and benzamide

ArticleYear
Poly(ADP-ribose) in the cellular response to DNA damage.
    Radiation research, 1985, Volume: 101, Issue:1

    Poly(ADP-ribose) polymerase is a chromatin-bound enzyme which, on activation by DNA strand breaks, catalyzes the successive transfer of ADP-ribose units from NAD to nuclear proteins. Poly(ADP-ribose) synthesis is stimulated by DNA strand breaks, and the polymer may alter the structure and/or function of chromosomal proteins to facilitate the DNA repair process. Electronmicroscopic studies show that poly(ADP-ribose) unwinds the tightly packed nucleosomal structure of isolated chromatin. Recent studies also show that the presence of poly(ADP-ribose) enhances the activity of DNA ligase. This may increase the capacity of the cell to complete DNA repair. Inhibitors of poly(ADP-ribose) polymerase or deficiencies of the substrate, NAD, lead to retardation of the DNA repair process. When DNA strand breaks are extensive or when breaks fail to be repaired, the stimulus for activation of poly(ADP-ribose) persists and the activated enzyme is capable of totally consuming cellular pools of NAD. Depletion of NAD and consequent lowering of cellular ATP pools, due to activation of poly(ADP-ribose) polymerase, may account for rapid cell death before DNA repair takes place and before the genetic effects of DNA damage become manifest.

    Topics: Benzamides; Cells, Cultured; DNA Repair; Enzyme Activation; Humans; Methylnitronitrosoguanidine; Niacinamide; Nucleoside Diphosphate Sugars; Poly Adenosine Diphosphate Ribose; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Ultraviolet Rays

1985

Other Studies

11 other study(ies) available for methylnitronitrosoguanidine and benzamide

ArticleYear
The monofunctional alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine triggers apoptosis through p53-dependent and -independent pathways.
    Toxicology and applied pharmacology, 2005, Jan-01, Volume: 202, Issue:1

    One of the cellular responses to DNA damaging events is the activation of programmed cell death, also known as apoptosis. Apoptosis is an important process in limiting tumorigenesis by eliminating cells with damaged DNA. This view is reinforced by the finding that many genes with pro-apoptotic function are absent or altered in cancer cells. The tumor suppressor p53 performs a significant role in apoptotic signaling by controlling expression of a host of genes that have pro-apoptotic or pro-survival function. The S(N)1 DNA alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) triggers apoptosis and the upregulation/phosphorylation of p53; however, the mechanism(s) governing MNNG-induced cell death remain unresolved. We observed that the human lymphoblastoid cell line WTK-1, which expresses mutant p53, shows far less sensitivity to the cytotoxic effects of MNNG than the closely related, p53-normal line TK-6. Exposure to 15 muM MNNG (LD50 at 24 h in TK-6) leads to a kinetically slower rate of apoptotic onset in WTK-1 cells compared to TK-6 as judged by viability assays and approaches that directly examine apoptotic onset. Similar results were obtained using an unrelated human lymphoblastoid line B310 expressing reduced levels of p53 due to E6 oncoprotein expression, indicating that MNNG activates both p53-dependent and -independent apoptotic mechanisms and that these two mechanisms are discernable by the rates which they trigger apoptotic onset. We document, during time points corresponding to peak apoptotic response in TK6, WTK-1, B310, and B310-E6, that these cell lines show marked decreases in mitochondrial transmembrane potential and increases in cytochrome c within the cytosolic fraction of MNNG-treated cells. Consistent with these events, we observed that both caspase-9 and -3 are activated in our panel of lymphoblastoid cells after MNNG exposure. We also found, using both broad spectrum and specific inhibitors, that blocking caspase activity in TK-6 and B310 cells had a significant effect on apoptotic advance, but that this treatment had no effect on entry of WTK-1 or B310-E6 cells into apoptosis. Finally, the PARP inhibitors benzamide and 6(5H)-phenanthridinone exerted notable inhibition of PARP activity and the nuclear translocation of the mitochondrial protein AIF (apoptosis-inducing factor) in MNNG-treated cells; however, these compounds exhibited no detectable inhibitory effects on MNNG-induced death in human lymphoblastoid cells. These ob

    Topics: Apoptosis; Benzamides; Caspase 3; Caspase 9; Caspases; Cell Line; Checkpoint Kinase 2; Humans; Methylnitronitrosoguanidine; Mitochondria; Phenanthrenes; Poly(ADP-ribose) Polymerases; Protein Serine-Threonine Kinases; Tumor Suppressor Protein p53

2005
In situ staining for poly(ADP-ribose) polymerase activity using an NAD analogue.
    The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 1998, Volume: 46, Issue:11

    Poly(ADP-ribose) polymerase (PARP) is a highly abundant nuclear enzyme which metabolizes NAD, in response to DNA strand breakage, to produce chains of poly(ADP-ribose) attached to nuclear proteins. PARP activation has been implicated in ischemia/reperfusion injury, but its biological significance is not fully understood. We have modified an existing in situ method for detection of PARP activity by using an NAD analogue in which adenine is modified by an "etheno" (vinyl) bridge. Etheno-NAD serves as a PARP substrate in an initial enzymatic reaction; a specific antibody to ethenoadenosine is then used in an immunohistochemical reaction to detect the production of modified poly(ADP-ribose). The method produces strong and specific labeling of nuclei in which PARP has been activated, i.e., those in which DNA strand breaks have been produced, and the results can be analyzed by microscopy, flow cytometry, or colorimetry. The method is applicable to cultured cells in several formats and to frozen tissue sections. The particular characteristics of the new method may assist in future in situ studies of PARP activation.

    Topics: Animals; Benzamides; Brain; Bromodeoxyuridine; Cell Line; Humans; Immunoenzyme Techniques; Methylnitronitrosoguanidine; Mice; NAD; Nitroprusside; Poly(ADP-ribose) Polymerases; Pyrogallol; Rats; Staining and Labeling; Ultraviolet Rays

1998
Response of V79 cells to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatment: inhibition of poly(ADP-ribose) and topoisomerase activity.
    Mutation research, 1991, Volume: 249, Issue:1

    MNNG-induced killing of V79 cells has been found to be enhanced on inhibition of topoisomerase II activity by nalidixic acid and poly(ADP-ribose) polymerase synthesis by benzamide. Using these 2 inhibitors in conjunction after MNNG treatment, some overlap in the functions of these 2 enzymes was observed. Nalidixic acid and benzamide were found to suppress the yields of mutations and SCEs induced by MNNG. Benzamide was more effective in suppressing the mutation yield whereas nalidixic acid was more effective in suppressing SCEs. A model based on the relative requirement of topoisomerase and poly(ADP-ribose) for the repair of different types of damage has been proposed to explain the results.

    Topics: Adenosine Diphosphate Ribose; Animals; Benzamides; Cell Line; Cell Survival; Cricetinae; Cricetulus; Methylnitronitrosoguanidine; Mutagens; Mutation; Nalidixic Acid; Sister Chromatid Exchange; Topoisomerase II Inhibitors

1991
Potentiation of carcinogen-induced methotrexate resistance and dihydrofolate reductase gene amplification by inhibitors of poly(adenosine diphosphate-ribose) polymerase.
    Cancer research, 1990, Sep-15, Volume: 50, Issue:18

    Poly(ADP-ribosyl)ation of nuclear proteins is an immediate response of most eukaryotic cells to DNA strand breaks, as induced by carcinogen treatment. DNA amplification, on the other hand, can be induced in cell culture systems by chemical or physical carcinogens, too, reaching peak levels a few days after induction treatment. We have previously shown that 3-aminobenzamide, an inhibitor of poly(ADP-ribosyl)ation, potentiates carcinogen-induced simian virus 40 DNA amplification in hamster cells which served as a short-term model system (Bürkle et al., Cancer Res., 47: 3632-3636, 1987). Here we report that those results can be extended to the development of methotrexate (MTX) resistance associated with dihydrofolate reductase (DHFR) gene amplification in a different hamster cell line. (a) Treatment with the alkylating carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) 3 days before selection with 350 nM MTX induced the MTX resistance frequency by 17- to 100-fold, as expected. Addition of 3-aminobenzamide (0.1 to 1 mM) before MNNG treatment further potentiated the frequency of MTX resistance by up to 5-fold in a dose-dependent manner, parallel to a potentiation of cytotoxicity. MTX resistance frequency was potentiated not only relative to the decrease in cell survival but also in absolute terms. The same potentiation occurred after cotreatment with benzamide (1 mM), another poly(ADP-ribosyl)ation inhibitor, under conditions which precluded direct drug interactions. Benzoic acid, a noninhibitory analogue, had no effect on the MNNG-induced MTX resistance frequency. (b) Neither 3-aminobenzamide, nor benzamide, nor benzoic acid at 1 mM, respectively, had any effect on the spontaneous frequency of MTX resistance. (c) Individual MTX-resistant colonies were expanded to determine their DHFR gene copy number. The relative frequency of DHFR gene amplification was similar (14% versus 22%) whether clones were derived from cultures induced with MNNG alone or MNNG in the presence of 1 mM 3-aminobenzamide. We conclude that poly(ADP-ribosyl)ation should act as a negative regulatory factor in the induction of DNA amplification, since inhibition of poly(ADP-ribose) polymerase potentiates both MNNG-induced simian virus 40 DNA amplification, as shown previously, and MNNG-induced MTX resistance associated with DHFR gene amplification, as shown in this paper.

    Topics: Animals; Benzamides; Cricetinae; DNA Damage; Drug Resistance; Drug Synergism; Gene Amplification; Methotrexate; Methylnitronitrosoguanidine; Poly(ADP-ribose) Polymerase Inhibitors; Proto-Oncogenes; Tetrahydrofolate Dehydrogenase

1990
ADP-ribosylation of ADPR-transferase and topoisomerase I in intact mouse epidermal cells JB6.
    Biochemistry, 1989, Mar-07, Volume: 28, Issue:5

    Poly(ADP-ribosylation) [poly(ADPR)] is a posttranslational modification of chromosomal proteins that affects the structural and functional properties of chromatin. We have studied poly(ADPR) of ADPR-transferase and topoisomerase I in intact mouse epidermal cells JB6 (clone 41) by a combination of affinity chromatography on phenylboronate and immunoblotting with monoclonal antibodies against poly(ADPR) chains and polyclonal antibodies against ADPR-transferase and topoisomerase I, respectively. Constitutive, steady-state poly(ADPR) substitution of ADPR-transferase was estimated at 4% and that of topoisomerase I at 0.1%. Active oxygen produced extracellularly by xanthine-xanthine oxidase and the methylating agent N-methyl-N'-nitro-N-nitrosoguanidine transiently increased the level of poly(ADPR) substitution of these enzymes by a factor of 6-10. While the poly(ADPR) substitution of ADPR-transferase remained elevated after 60 min of incubation, the poly(ADPR) substitution of topoisomerase I had returned to control values within this time. Benzamide (100 microM) partially prevented the stimulation of poly(ADPR) synthesis by these agents. We speculate that self-inactivation of ADPR-transferase by poly(ADPR) represents a feedback mechanism that has the function to avoid excessive poly(ADPR) synthesis and concomitant NAD and ATP depletion. Inactivation of topoisomerase I in the neighborhood of DNA breakage may temporarily shut down DNA replication and allow DNA repair to occur.

    Topics: Animals; Antibodies, Monoclonal; Benzamides; Cells, Cultured; Chromatography, Affinity; DNA Topoisomerases, Type I; Immunoblotting; Methylnitronitrosoguanidine; Nucleoside Diphosphate Sugars; Oxygen; Poly Adenosine Diphosphate Ribose; Poly(ADP-ribose) Polymerases; Protein Processing, Post-Translational

1989
Influence of benzamide on killing and mutation of density-inhibited V79 cells by MNNG.
    Mutation research, 1989, Volume: 225, Issue:3

    Density-inhibited V79 cells when held for 24 h in complete medium after exposure to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) show improved survival levels and decreased mutant frequencies at all dose levels, compared to cells not so held. However, when benzamide, an inhibitor of poly(ADP-ribose) synthesis was present during this 24-h holding, the improvement in survival and decrease in mutant frequencies were not observed. Rather, compared to the control, the cells became more sensitive to MNNG and mutant frequency also increased significantly for all doses studied.

    Topics: Animals; Benzamides; Cell Line; Cell Survival; Contact Inhibition; Cricetinae; DNA Repair; Methylnitronitrosoguanidine; Mutation; Nucleoside Diphosphate Sugars; Poly Adenosine Diphosphate Ribose

1989
Induction of repair functions by hydrogen peroxide in Chinese hamster cells.
    International journal of radiation biology and related studies in physics, chemistry, and medicine, 1988, Volume: 53, Issue:6

    Hydrogen peroxide has been found to kill Chinese hamster V79 cells as an exponential function of dose. When a small dose (0.9 microgram/ml for 1 h) was used as a pretreatment, before exposure to higher concentrations of the same agent, the cells became more resistant to killing than those which were not so pretreated. The presence of cycloheximide or benzamide, during this pretreatment, inhibited this observed increase in resistance. This pretreatment also resulted in decreased killing efficiency by MNNG and gamma-rays, but had no effect upon UV-light-induced killing. The results suggest that proteins (repair enzymes?) are synthesized after treatment with the small dose of hydrogen peroxide, and that these induced proteins enhance the cellular repair functions for agents causing DNA breaks.

    Topics: Animals; Benzamides; Cell Line; Cell Survival; Cricetinae; Cricetulus; Cycloheximide; DNA Repair; Gamma Rays; Hydrogen Peroxide; Methylnitronitrosoguanidine; Radiation Tolerance; Ultraviolet Rays

1988
Mechanism of alteration of poly(adenosine diphosphate-ribose) metabolism by hyperthermia.
    Cancer research, 1988, Aug-01, Volume: 48, Issue:15

    The effects of hyperthermia on adenine nucleotide metabolism including NAD and poly(ADP-ribose) have been studied in confluent cultures of C3H10T1/2 cells. Cells replated immediately following hyperthermic treatment showed only 9% survival relative to controls while after a 24-h recovery period at 37 degrees C survival was 87% of control. Hyperthermic treatment caused no detectable effect on total cellular levels of either NAD or ATP but produced a prolonged increase in cellular content of poly(ADP-ribose). Studies of the mechanism of this effect show that a major alteration of poly(ADP-ribose) metabolism caused by hyperthermia involves a decrease in the rate of turnover of polymers of ADP-ribose. Normal polymer turnover rates were restored during recovery at 37 degrees C even in the presence of cyclohexamide. The results argue that poly(ADP-ribose) glycohydrolase activity is reversibly altered by hyperthermia. Inhibition of poly(ADP-ribose) synthesis following hyperthermia delays recovery of normal rates of protein synthesis and recovery of the ability of the cells to plate and form colonies.

    Topics: Adenosine Triphosphate; Animals; Benzamides; Fever; Glycoside Hydrolases; Methylnitronitrosoguanidine; Mice; Mice, Inbred C3H; NAD; Nucleoside Diphosphate Sugars; Poly Adenosine Diphosphate Ribose

1988
Further evidence for a different mode of action of caffeine and benzamide on mammalian cells.
    Mutation research, 1987, Volume: 192, Issue:1

    Post-treatment with 2 mM caffeine or 2 mM benzamide increased the lethality of MNNG (N-methyl-N'-nitro-N-nitrosoguanidine) treated V79 cells; in the presence of 50 microM deoxycytidine, the caffeine effect was eliminated whereas the benzamide effect remained the same. Combined treatment with caffeine/benzamide alone produced a large amount of cell lethality which was eliminated by 50 microM deoxycytidine. Benzamide produced a strong inhibition of the poly(ADP-ribose)polymerase activity present in cell-free extracts prepared from V79 cells with greater than 90% inhibition at 2 mM concentration; caffeine on the other hand did not produce any substantial inhibition of this activity in the 2-5 mM range. These results further substantiate our earlier hypothesis that the mode of action of caffeine and benzamide on eukaryotic cells containing DNA damage are not identical [S.K. Das, C.C. Lau and A.B. Pardee (1984) Mutation Res., 131, 71-79].

    Topics: Animals; Benzamides; Caffeine; Cell Line; Cell Survival; Cricetinae; DNA Repair; Drug Synergism; Methylnitronitrosoguanidine; Poly(ADP-ribose) Polymerases

1987
Relationship between DNA strand breaks and inhibition of poly (ADP-ribosylation): enhancement of carcinogen-induced transformation.
    Carcinogenesis, 1986, Volume: 7, Issue:2

    Inhibition of poly(ADP-Rib) by benzamide (BA) or 3-amino-benzamide (3AB) for a limited period (i.e., when ADP-ribosylation is elevated) during and shortly following X-ray or MNNG-induced DNA damage of BALB/3T3 cells significantly (3- to 30-fold) enhanced transformation frequency by these agents. Individual Type III foci isolated from benzamide, X-ray, or X-ray plus benzamide treated cultures were established and characterized for growth in soft agar and for tumor induction in nude mice. DNA isolated from representative transformed lines established as a result of BA, X-ray or X-ray and BA treatments was transfected onto NIH/3T3 cells. Transformation efficiencies ranging from 0.17 to 0.28 foci/micrograms of DNA were observed suggesting the possibility that dominant transforming gene(s) were responsible for the oncogenic phenotype of radiation and benzamide transformed DNA.

    Topics: Animals; Base Sequence; Benzamides; Cell Survival; Cell Transformation, Neoplastic; Cells, Cultured; DNA; DNA, Neoplasm; Methylnitronitrosoguanidine; Mice; NAD; Oncogenes; Poly(ADP-ribose) Polymerase Inhibitors

1986
Poly(ADP-ribose) Polymerase inhibitors preserve nicotinamide adenine dinucleotide and adenosine 5'-triphosphate pools in DNA-damaged cells: mechanism of stimulation of unscheduled DNA synthesis.
    Biochemistry, 1983, Oct-25, Volume: 22, Issue:22

    Inhibitors of poly(ADP-ribose) polymerase stimulated the level of DNA, RNA, and protein synthesis in DNA-damaged L1210 cells but had negligible effects in undamaged L1210 cells. The poly(ADP-ribose) polymerase inhibitors stimulated DNA repair synthesis after cells were exposed to high concentrations of N-methyl-N'-nitro-N-nitrosoguanidine (68 and 136 microM) but not after exposure to low concentrations (13.6 and 34 microM). When the L1210 cells were exposed to 136 microM N-methyl-N'-nitro-N-nitrosoguanidine, the activation of poly(ADP-ribose) polymerase resulted in the rapid depletion of oxidized nicotinamide adenine dinucleotide (NAD+) levels and subsequent depletion of adenosine 5'-triphosphate (ATP) pools. After low doses of N-methyl-N'-nitro-N-nitrosoguanidine (13.6 microM), there were only small decreases in NAD+ and ATP. Poly(ADP-ribose) polymerase inhibitors prevented the rapid fall in NAD+ and ATP pools. This preservation of the ATP pool has a permissive effect on energy-dependent functions and accounts for the apparent stimulation of DNA, RNA, and protein synthesis. Thus, the mechanism by which poly(ADP-ribose) polymerase inhibitors stimulate DNA, RNA, and protein synthesis in DNA-damaged cells appears to be mediated by their ability to prevent the drastic depletion of NAD+ pools that occurs in heavily damaged cells, thereby preserving the cells' ability to generate ATP and maintain energy-dependent processes.

    Topics: Adenosine Triphosphate; Animals; Benzamides; Cells, Cultured; DNA; DNA Repair; DNA, Neoplasm; Leukemia L1210; Methylnitronitrosoguanidine; Mice; NAD; NAD+ Nucleosidase; Neoplasm Proteins; Niacinamide; Poly(ADP-ribose) Polymerase Inhibitors; RNA, Neoplasm

1983
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