Abstract:
:N-Hydroxyethylnitroso-N'-ethylurea (HEENU) and N-hydroxyethylnitroso-N'-chloroethylurea (HCNU) are two of the few nitrosoureas which induce hepatocellular tumours in rats without further treatment. In the present study we have investigated whether this is due to selectively elevated levels of DNA hydroxyethylation in the target tissue. Formation of the promutagenic base O6-hydroxyethyldeoxyguanosine (O6-HEdG) in various rat tissues was determined by immuno-slot-blot assay. After a single dose by gavage (0.36 mmol/kg body wt) of HEENU, initial levels of O6-HEdG in liver and brain were close to the detection limit of 1.5 mumol/mol deoxyguanosine. In liver, steady state concentrations of 3.5 mumol/mol were reached after 6 h and maintained for at least 18 h. In brain, O6-HEdG levels were 1.7 mumol/mol after 6 h and 3.0 mumol/mol after 24 h. In a second experiment, the formation of O6-HEdG was assessed in target and non-target tissues 6 h after a single dose by gavage (0.36 mmol/kg) of HEENU, HCNU or hydroxyethylnitrosourea (HENU), which is not hepatocarcinogenic. The extent of DNA hydroxyethylation was greatest with HENU in all tissues examined. Concentrations of O6-HEdG were highest in liver (37.2 mumol/mol), followed by kidney (23.3 mumol/mol), lung (18.9 mumol/mol), brain (6.8 mumol/mol) and testes (3.8 mumol/mol). With HEENU and HCNU, levels of 1.4-3.3 mumol O6-HEdG/mol dG were observed in all tissues. In vitro, the alkylation reactions for all three compounds were nearly complete within 6 h. On a molar basis, yields of O6-HEdG in vitro were similar for HENU and HCNU and 3.7 times lower for HEENU. This suggests that the in vivo reactions of the dialkylnitrosoureas are by pathways other than or in addition to those occurring in vitro. We conclude that the hepatocarcinogenicity of HCNU and HEENU cannot be explained on the basis of their reaction with cellular DNA.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Ludeke B,Schubert M,Yamada Y,Lijinsky W,Kleihues Pdoi
10.1016/0009-2797(91)90083-jsubject
Has Abstractpub_date
1991-01-01 00:00:00pages
207-16issue
2eissn
0009-2797issn
1872-7786pii
0009-2797(91)90083-Jjournal_volume
79pub_type
杂志文章abstract::The caseinate and glycated caseinate generated from the transglutaminase-catalyzed reaction of caseinate and oligochitosan were digested using pepsin and trypsin, and the activity of the resultant digests was measured in rat intestinal epithelial cell line (IEC-6) using several biological responses as indicators. Comp...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2020.109201
更新日期:2020-09-01 00:00:00
abstract::Irinotecan is highly effective in the treatment of metastatic colorectal cancer as well as many other cancers. However, irinotecan is known to cause severe diarrhea, which pose significant problems in patients undergoing irinotecan based chemotherapy. Dietary and herbal components have shown promise in improving gastr...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2018.06.018
更新日期:2018-08-01 00:00:00
abstract::Thiol oxidation by diphenyl ditelluride is a favorable reaction and may be responsible for alteration in regulatory or signaling pathways. We have measured rate constants for reactions of diphenyl ditelluride with cysteine, dimercaptosuccinic acid, glutathione and dithiothreitol in phosphate buffer. The relative react...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2008.12.013
更新日期:2009-06-15 00:00:00
abstract::Metabolism is a prerequisite for the development of benzene-mediated myelotoxicity. Benzene is initially metabolized via cytochromes P450 (primarily CYP2E1 in liver) to benzene-oxide, which subsequently gives rise to a number of secondary products. Benzene-oxide equilibrates spontaneously with the corresponding oxepin...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2009.12.025
更新日期:2010-03-19 00:00:00
abstract::In Alzheimer's disease (AD) a reduction in acetylcholinesterase (AChE) and an increase in butyrylcholinesterase (BChE) activity are observed. K variant (539T) is the most common variant of the BCHE gene and, although controversial, several studies reported association between K variant and AD. Previous results showed ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2012.09.008
更新日期:2013-03-25 00:00:00
abstract::4-Hydroxy-2-nonenal (HNE), a major reactive product of lipid peroxidation, is believed to play a central role in atherogenic actions triggered by oxidized lipoproteins. An aldo-keto reductase (AKR) 1C15 efficiently reduces HNE and is distributed in many rat tissues including endothelial cells. In this study, we invest...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2010.12.018
更新日期:2011-05-30 00:00:00
abstract::The interaction of nanoparticles (NPs) with proteins is a topic of high relevance for the medical application of nanomaterials. In the study, a comprehensive investigation was performed for the binding properties of silver nanoparticles (AgNPs) to pepsin. The results indicate that the binding of AgNPs to pepsin may be...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2018.03.004
更新日期:2018-04-25 00:00:00
abstract::In the series of tetraalkylammonium ions from tetramethylammonium to tetra-n-heptylammonium, tetra-n-pentylammonium ion was a potent protector of both murine L1210 leukemia and bone marrow progenitor cells against mechlorethamine cytotoxicity. It was also a non-competitive inhibitor of choline uptake. Phosphonium anal...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(82)90095-3
更新日期:1982-06-01 00:00:00
abstract::Inhibition of microtubule assembly by arenastatin A (1) and five synthetic analogs (3-7) was examined. Arenastatin A and the triamide 6 showed potent and moderately strong inhibitory activities, respectively (IC50; 2.3 microM for 1, 7.8 microM for 6) and also depolymerized preformed microtubules. The other analogs tes...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(96)03743-x
更新日期:1996-12-20 00:00:00
abstract::The in vitro metabolism of p-nitroanisole, aminopyrine, and aniline by rat liver microsomal monoxygenases were studied in the presence of different polychlorinated biphenyl (PCB) mixtures and some related hydroxybiphenyls. The tested PCB mixtures contained preferably dichloro- (di-CB), tetrachloro- (tetra-CB), or hexa...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(77)90128-4
更新日期:1977-02-01 00:00:00
abstract::MicroRNAs (miRNAs) have been regarded as potential modulators in varying ocular diseases, including age-related cataract (ARC). However, the roles of miR-221 in ARC progression and its underlying mechanism remain poorly understood. In this study, human lens epithelial cell line (SRA01/04) was used to investigate the p...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2019.03.021
更新日期:2019-06-01 00:00:00
abstract::Toxicokinetics of trichloroethylene (TCE) and tetrachloroethylene (PER) in culture medium and their toxicity to CHO-K1 cells were investigated by employing an in vitro vapor exposure system. Cells were cultured in a 60 mm petri dish with a 25 mm glass dish glued in the central area. TCE or PER was added to the central...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(01)00226-5
更新日期:2001-08-31 00:00:00
abstract::The present study was aimed to investigate the effects of ethylene glycol (EG) on serum marker enzymes, antioxidant defense systems and lipid peroxidation concentration (malondialdehyde=MDA) in various tissues of rats exposed to ethylene glycol. EG (1.25% or 2.5%) in drinking water was administered orally to rats (Spr...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2007.02.007
更新日期:2007-04-25 00:00:00
abstract::The main goal of the present study was to obtain insight into depot formation and penetration following percutaneous VX poisoning, in order to identify an appropriate decontamination window that can enhance or support medical countermeasures. The study was executed in two phases, using the hairless guinea pig as an an...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2016.02.001
更新日期:2017-04-01 00:00:00
abstract::Despite the great progress made in setting the basis for the molecular diversity of acetylcholinesterase (AChE), an explanation for the existence of two types of amphiphilic subunits, with and without glicosylphosphatidylinositol (GPI) (Types I and II), has not been provided yet. In searching whether, as for the defic...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2008.04.018
更新日期:2008-09-25 00:00:00
abstract::Acetaldehyde (AA) and methylglyoxal (MG) are reactive, ubiquitous aldehydes, present in the environment and endogenously formed in animals and humans. They have both been shown to readily form DNA adducts under simulated physiological conditions. We report here on the use of cultured normal and SV40T antigen-immortali...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(97)00107-5
更新日期:1998-01-30 00:00:00
abstract::Polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene (BaP) are widely-distributed environmental contaminants known to exert toxic effects in various tissues, including placenta. PAHs have notably been shown to inhibit proliferation of trophoblastic cells. The present study was designed to determine whether P...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2013.12.004
更新日期:2014-03-05 00:00:00
abstract::Quaternary ammonium compounds (e.g., benzalkonium chloride (BAC) and cetylpyridinium chloride (CPC)) constitute a group of cationic surfactants are widely used for personal hygiene and medical care despite the potential pulmonary toxicity. To examine whether BAC and CPC aerosols deposited in the alveolar region alter ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2020.108962
更新日期:2020-02-01 00:00:00
abstract::Locoism threatens the sustainable development of animal husbandry in areas around the world with intensified desertification, especially in the western United States, western China, Canada, and Mexico, among other countries. This study was conducted to discover potential serum biomarkers in locoweed-poisoned rabbits a...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2017.02.022
更新日期:2017-04-25 00:00:00
abstract::Selenium compounds such as methylseleninic acid (MSA) and sodium selenite (SS) have been widely evaluated as potential anti-cancer agents in the clinical setting. Primary effusion lymphoma (PEL) is a non-Hodgkin's B-cell lymphoma, associated with immunosuppressed individuals, such as post-transplant or AIDS patients. ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2017.01.027
更新日期:2017-03-25 00:00:00
abstract::Sophoricoside (SOPH) is an isoflavone glycoside isolated from the fruits of Sophora japonica. Since its first isolation in 1961, there are rare findings about the effects of SOPH on reproductive system. In the present study, the pregnant mice administrated by different doses of SOPH were used to explore the effect of ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2014.05.009
更新日期:2014-08-05 00:00:00
abstract::Previous investigations have shown that the carcinogen vinyl chloride causes base-pair substitution in the bacterium Salmonella typhimurium. The ability of four conceivable metabolites-chloroethylene oxide, chloroacetaldehyde, 2-chloroethanol and chloroacetic acid-to cause base-pair substitution directly in Salmonella...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(76)90041-7
更新日期:1976-03-01 00:00:00
abstract::Methylene diphenyl diisocyanate (MDI) is among the leading chemical causes of occupational asthma world-wide, however, the mechanisms of disease pathogenesis remain unclear. This study tests the hypothesis that glutathione (GSH) reacts with MDI to form quasi-stable conjugates, capable of mediating the formation of MDI...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2013.06.005
更新日期:2013-09-05 00:00:00
abstract::This paper reports on time-resolved microfluorimetric measurements on hematoporphyrin-derivative (HpD)-treated lymphocytes. HpD is at present widely used as a tumor-locating and photosensitizing drug. It is therefore of great importance to study the extent to which the HpD uptake process depends on cell functional and...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(84)90090-5
更新日期:1984-07-01 00:00:00
abstract::Polo-like kinase 1 (PLK1) is a prominent mediatory player during the cell cycle, mitosis, and cytokinesis in eukaryotic cells. Besides its physiological roles, PLK1 expression is upregulated in a wide range of human malignant tumors and its overexpression worsens prognosis, therefore, specific inhibition of PLK1 in tu...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2020.109288
更新日期:2020-12-01 00:00:00
abstract::The asymmetric A12 acetylcholinesterase (AChE) molecular form, consisting of three tetrameric catalytic oligomers and three non-catalytic subunits of collagen Q (ColQ), is the functional AChE form in the neuromuscular junction. Its extremely high concentration and sharp localization in the junction is mostly due to th...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2005.10.008
更新日期:2005-12-15 00:00:00
abstract::The cytochrome P450 expression profile was determined in the MCF10A human breast epithelial cell line, as was the ability of this cell line to catalyze the bioactivation of the cooked food mutagen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Using non-quantitative reverse transcription-polymerase chain rea...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2006.01.007
更新日期:2006-04-15 00:00:00
abstract::There are global increased interests to identify novel agents that can possess anti-tumor effects or maximize the anti-tumor effects of low doses for conventional anti-cancer drugs. The aim of this study was to investigate anti-tumor effects and protective role of isolated hesperidin from sweet orange on doxorubicin-i...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2018.02.029
更新日期:2018-04-01 00:00:00
abstract::Tiaprofenic acid is a widely used anti-inflammatory drug; however, the reductive metabolism of tiaprofenic acid is not yet well understood. Here, we compared the reduction of tiaprofenic acid in microsomes and cytosol from the human liver. The microsomes exhibited lower Km value toward tiaprofenic acid than the cytoso...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2017.03.006
更新日期:2017-10-01 00:00:00
abstract::4-Methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) has been identified as one of the strongest nitrosamine carcinogens in tobacco products in all species tested. Carbonyl reduction to 4-methylnitrosamino-1-(3-pyridyl)-1-butanol (NNAL) followed by glucuronosylation is considered to be the main detoxification pathway in...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(00)00304-5
更新日期:2001-01-30 00:00:00