Disease relevance of TRIAZIQUONE

• In this study we have investigated the molecular mechanisms for trenimon-induced toxicity in aerobic versus hypoxic conditions with the use of freshly isolated rat hepatocytes [1].
• In view of the known correlations between plasma membrane functions and the regulation of cell division, it is proposed that the growth inhibition by Trenimon of Ehrlich ascites tumor cells may be caused by its interaction with the plasma membrane [2].
• Distribution of open gaps and breaks is highly correlated with chromosome length and distribution of breaks involved in chromatid translocations in Fanconi's anemia and in Trenimon-treated cells [3].
• NMRI mice (female female) were treated with 0.25 mg/kg body weight Trenimon (2,3,5-triethyleneiminobenzoquinone-1,4) in the preovulatory phase just before ovulation [4].
• Different sensitivity of diploid and trisomic cells from patients with Down syndrome mosaic after treatment with the trifunctional alkylating agent trenimon [5].

High impact information on TRIAZIQUONE

• Modulation of trenimon-induced cytotoxicity by DT-diaphorase in isolated rat hepatocytes under aerobic versus hypoxic conditions [1].
• Inactivation of hepatocyte DT-diaphorase by dicumarol under hypoxic conditions increased trenimon-induced cytotoxicity by approximately 3.5-fold and increased semiquinone radical levels 2-fold without affecting its reduction rate [1].
• Effects of conjugated and nonconjugated antithymocyte globulin and trenimon on T lymphocytes and skin graft rejection [6].
• Trenimon (Tr) was bound covalently to antithymocyte globulin (ATG) and the effects of the complex on peripheral blood cells, thymus cells, spleen cells, and on foreign skin graft rejection assessed [6].
• The results clearly show that dominant lethality is dose dependent for Trenimon- or PDMT-treated chromosomes in mature sperm and mature oocytes, and an increased amount of chromosomal material per nucleus yields an enhanced lethality [7].

Chemical compound and disease context of TRIAZIQUONE

• Cytogenetic studies confirmed the clinical diagnosis and revealed a spontaneous chromosomal instability and hypersensitivity to the cross-linking agents diepoxybutane and Trenimon [8].

Biological context of TRIAZIQUONE

• The following evidence suggests the mechanisms for trenimon detoxification involves reduction by DT-diaphorase, while the cytotoxic mechanism involves macromolecular alkylation under hypoxic conditions as well as oxidative stress under aerobic conditions [1].
• Spontaneous and trenimon-induced sister chromatid exchange (SCE) frequencies were determined in second mitoses occurring at 66 h, 78 h, 90 h, and 102 h after culture start [9].
• Of the unfertilized oocytes 76.2% deriving from mice treated with 0.25 mg/kg Trenimon, were aberrant in the stage of metaphase II (Röhrborn and Hansmann, 1971) [4].
• In the trenimon-treated series a clear cell cycle delay was detected as compared with the normal distribution of different types of mitoses found in series treated with BUdR only [9].
• The mice used for air-dried preparations were treated with hyroxyurea and triaziquone, which reduces the spermatocyte population to a small, well-defined group of cells in meiotic interphase [10].

Anatomical context of TRIAZIQUONE

• Induced dominant lethal mutations and cytotoxic effects in germ cells of Drosophila melanogaster with Trenimon, PDMT and sodium monofluorophosphate [7].
• The protective activity of the combined application of anticlastogens against the chromosome-damaging action of Trenimon and bleomycin was studied by analyzing more than 32000 metaphases from cultures of human peripheral lymphocytes [11].
• Here we show that a significant increase in the frequency of Trenimon induced sister chromatid exchanges (SCEs) and chromosome aberrations can be found in trisomic lymphocytes and fibroblasts as compared to disomic cells [5].
• Human leukocyte cultures were pulse-treated with the trifunctional alkylating mutagen trenimon in a final concentration of 10(-7) M for 15--20 h after culture start, i.e., in the G1 phase of the cell cycle [9].
• Frequencies of dead fetuses per pregnancy in the ethanol- and Trenimon-treated groups were increased approximately 2.5- and 4-fold, respectively, over the control value of approximately 16% [12].

Associations of TRIAZIQUONE with other chemical compounds

• Inhibition of hepatocyte DT-diaphorase by dicumarol increased trenimon-induced cytotoxicity by approximately 10-fold, and markedly inhibited hydroquinone formation [1].
• Effects of caffeine on sister chromatid exchange (SCE) after exposure to UV light or triaziquone studied with a fluorescence plus giemsa (FPG) technique [13].
• Human peripheral lymphocytes and Chinese hamster ovary cells were treated in the G1 phase of the cell cycle with the trifunctional alkylating agent trenimon (TRN) and post-treated with a single-strand specific endonuclease from Neurospora crassa (NE) [14].
• Continuous fluoride treatment also protected the cells from Trenimon-induced damage, but the effect was not significant, possibly because of heavily damaged mitoses which appeared under these conditions [15].
• Pretreatment of HPLs with trenimon (TRN), diepoxybutane (DEB), or methylnitrosourea (MNU) in the G0 phase of the cell cycle results in dose-dependent elevations of the SCE frequencies [16].

Gene context of TRIAZIQUONE

• Genetical analysis of the yeast insert DNAs revealed three genes SNG1, SNQ2, and SNQ3 that confer the phenotype hyper-resistance to MNNG, to 4-NQO and triaziquone, and to mutagens 4-NQO, MNNG, and triaziquone, respectively [17].
• Trenimon at highly toxic concentrations had no effect on the fluidity of phospholipid membranes or of membranes of Ehrlich ascites tumour cells as analysed by ESR spin-label methods [18].
• T(1;13)70H/+ male mice were treated with hydroxyurea (HU) and Trenimon (T) [19].
• (1982) from the frequencies of reunion figures between specific chromosomes as observed in chromosome instability syndromes (Fanconi anemia, Bloom syndrome) and after treatment with Trenimon [20].
• Inhibition of DT-diaphorase by dicoumarol markedly inhibited the cytotoxic activity of trenimon to the resistant L5178Y/HBM10 cells [21].

Analytical, diagnostic and therapeutic context of TRIAZIQUONE

• Continuous treatment of the cells with 10(-3) M NaF had no effect on [3H]TdR labelling or mitotic indices in otherwise untreated cultures, but led to an impressive effect on DNA synthesis in Trenimon-treated cultures, without a considerable effect on the mitotic indices [15].
• Ethanol and Trenimon treatments produced approximately 3- and 7-fold increases, respectively in the frequencies of preimplantational loss over that seen for the control group (7.3%), resulting in significant ethanol and Trenimon effects (p less than 0.001) [12].
• Treatment of the cells in G1 from 15-20 h with 0.5 X 10(-6) M Trenimon resulted in a considerable cell cycle delay, as measured by [3H]-TdR autoradiography and determination of mitotic indices [15].
• In spite of treatment of the sarcoma 180 with triaziquone over 50 passages, no resistance could be detected against triaziquone either in the in vitro test or in animal experiments [22].
• Isolated perfusion of normal kidneys with tris-ethylenimino-benzochinon (triaziquon, Trenimon) and amethopterin (Methotrexate) demonstrated that the kidney tolerates far higher antitumor drug concentrations than are achieved by systemic anticancer chemotherapy [23].

References