Disease relevance of Bioxirane

• FA cells show increased chromosome breakage and hypersensitivity to DNA cross-linking agents such as diepoxybutane and mitomycin C [1].
• Cells derived from FA patients show elevated levels of chromosomal breakage and an increased sensitivity to bifunctional alkylating agents such as mitomycin C (MMC) and diepoxybutane (DEB) [2].
• However, their spleen cells had dramatically increased numbers of chromosomal aberrations in response to MMC and DEB [2].
• Transfection of normal human and Chinese hamster DNA corrects diepoxybutane-induced chromosomal hypersensitivity of Fanconi anemia fibroblasts [3].
• Unlike the lymphoblasts, this myeloid leukemia cell line (UoC-M1) was hypersensitive to mitomycin-C (MMC) and diepoxybutane (DEB) and exhibited a marked decrease in nuclear FANCA, FANCG, and FANCD2-L [4].

Psychiatry related information on Bioxirane

• In order to study individual differences in response to the genotoxicity of diepoxybutane, we devised a human lymphocyte culture system that involves short-term culture of T lymphocytes and measurement of sister chromatid exchange (SCE) and chromosomal aberration frequency as genotoxic end-points [5].

High impact information on Bioxirane

• FA cells exhibit chromosomal instability and hyper-responsiveness to the clastogenic and cytotoxic effects of bifunctional alkylating (cross-linking) agents, such as diepoxybutane (DEB) and mitomycin C (MMC) [6].
• The two kinds of selectively labelled 80S ribosomes were treated with diepoxybutane at low concentration [7].
• Brief exposures to nontoxic levels of methylnitrosourea, diepoxybutane, mitomycin C, hydroxyurea, doxorubicin, and UV light stimulated LOH at all loci at frequencies ranging from 1-8 x 10(-3) per cell (10-123 times higher than in untreated cells) [8].
• Cultured cells derived from chromosomally normal fetuses which served as controls did not show DEB-induced chromosome breakage [9].
• The increased sensitivity of FA cells to DNA cross-linking agents such as mitomycin C (MMC) and diepoxybutane (DEB), including the induction of chromosomal aberrations and delay in the G2 phase of the cell cycle, have suggested a role for the FA genes in DNA repair, cell cycle regulation, and apoptosis [10].

Chemical compound and disease context of Bioxirane

• Cultured cells from individuals affected with Fanconi anemia (FA) exhibit spontaneous chromosome breakage and hypersensitivity to the cell killing and clastogenic effects of the difunctional alkylating agent diepoxybutane (DEB) [3].
• Human glutathione S-transferase T1-1 enhances mutagenicity of 1,2-dibromoethane, dibromomethane and 1,2,3,4-diepoxybutane in Salmonella typhimurium [11].
• 1,3-Butadiene and two major genotoxic metabolites 3,4-epoxybutene (EB) and 1,2:3,4-diepoxybutane (DEB) were used as model compounds to determine if genetic toxicity findings in animal and human cells can aid in extrapolating animal toxicity data to man [12].
• Work described here indicates that arsenite specifically potentiates chromosomal aberrations induced by a DNA crosslinking agent, 1,3-butadiene diepoxide, but does not effect the induction of sister chromatid exchanges under the same treatment conditions [13].
• Three metabolites of 1,3-butadiene, namely butadiene diolepoxide, butadiene monoepoxide and diepoxybutane, were tested in the bacterial mutation assay using Salmonella typhimurium strain TA100 with and without metabolic activation (S9 mix) [14].

Biological context of Bioxirane

• The current diagnostic test for FA consists of cytogenetic quantitation of chromosomal breakage in response to diepoxybutane (DEB) or mitomycin C (MMC) [15].
• Although a variable phenotype makes accurate diagnosis on the basis of clinical manifestations difficult in some patients, study of cellular sensitivity to the clastogenic effect of DNA cross-linking agents such as diepoxybutane (DEB) has been used to facilitate the diagnosis [16].
• Comparative evaluation of diepoxybutane sensitivity and cell cycle blockage in the diagnosis of Fanconi anemia [17].
• In a previous study, we observed a bimodal distribution of sensitivity to sister chromatid exchange (SCE) induction by diepoxybutane (DEB) in lymphocytes from healthy individuals [18].
• Repair kinetics of DNA interstrand cross-link production and removal was measured by alkaline elution for AA8 and mutants UV4 and UV5 after exposure to diepoxybutane [19].

Anatomical context of Bioxirane

• The mutagenic potential and mutational spectra of butadiene (BD), 1,2-epoxybutene (EB), and diepoxybutane (DEB) were determined in splenic T cells from exposed B6C3F1 mice [20].
• Only mouse liver microsomes displayed quantifiable rates for metabolism of BMO to butadiene diepoxide (Vmax = 0.2 nmol/mg protein/min), a known rodent carcinogen [21].
• Adenine adducts with diepoxybutane: isolation and analysis in exposed calf thymus DNA [22].
• Likewise, UDS in rat and mouse hepatocytes in vitro was not induced by EB or DEB [12].
• Amniotic fluid cells from 30 fetuses from 24 families were monitored for baseline and diepoxybutane-induced chromosomal breakage [23].

Associations of Bioxirane with other chemical compounds

• Fibroblast survival studies using four clastogens (bleomycin, diepoxybutane, mitomycin-c, and 4-nitroquinoline-1-oxide) and gamma radiation showed no significant difference between DC and normal fibroblasts [24].
• The individual genotoxic response of cultured human lymphocytes to diepoxybutane (DEB), an epoxide metabolite of 1,3-butadiene, shows a bimodal distribution [25].
• Sister chromatid exchanges (SCEs) were either reduced or unchanged after exposure to MMC, while another bi-functional alkylating agent, diepoxybutane (DEB), induced an increase in SCE level at a low, equitoxic dosage in parallel experiments [26].
• We have examined cross-linking by 1,2,3,4-diepoxybutane (DEB) and 1,2,7,8-diepoxyoctane (DEO) within a fragment of the 5S RNA gene of Xenopus borealis in both the free and nucleosomal states [27].
• While only slight but significant differences could be detected of the average spontaneous, DEB- and bleomycin (G2)-induced chromosome breakage between patient and control lymphocytes, individual patients and two of the control individuals showed a more distinct increase in the frequency of the studied end points [28].

Gene context of Bioxirane

• Influence of GSTT1, mEH, CYP2E1 and RAD51 polymorphisms on diepoxybutane-induced SCE frequency in cultured human lymphocytes [29].
• Additional experiments revealed that yeast RAD52 gene expression increased the level of resistance to the DNA damaging agents diepoxybutane, and methyl methanesulfonate, but did not alter sensitivity to ultraviolet radiation [30].
• Mitomycin C and diepoxybutane action mechanisms and FANCC protein functions: further insights into the role for oxidative stress in Fanconi's anaemia phenotype [31].
• Contrary to previous findings with DEB and MEB, the polymorphic GSTM1 and GSTT1 do not appear to be involved in the detoxification of EBD in human lymphocytes [32].
• However, when cells were exposed to the DNA-cross-linking agent, diepoxybutane, overexpression of wild-type menin inhibited DNA synthesis [33].

Analytical, diagnostic and therapeutic context of Bioxirane

• Cross-linked amino acids in the protein pairs L3-L19 and L23-L29 of Bacillus stearothermophilus ribosomes after treatment with diepoxybutane [34].
• Butadiene-exposed workers did not differ, however, from unexposed workers with respect to frequency of uninduced or diepoxybutane-induced sister chromatid exchanges, aneuploidy as measured by fluorescence in situ hybridization of chromosomes 1, 7, 8 and 12, glycophorin A variants or lymphocyte hprt somatic mutation [35].
• Liquid chromatography (LC) in combination with tandem mass spectrometry (MS/MS) and stable isotope methodology was employed for the analysis of the N7-guanine (Gua) adducts derived from 1,2:3, 4-diepoxybutane (BDO2) a reactive metabolite of 1,3-butadiene (BD) [36].
• Analysis of butadiene, butadiene monoxide, and butadiene dioxide in blood by gas chromatography/gas chromatography/mass spectroscopy [37].
• The tumors from diepoxybutane-treated cell cultures were composed of highly anaplastic giant cells with centrally located cytoplasmic inclusions [38].

References