Abstract:
:The cytotoxicity and cardiotoxicity of benzoyl mustard (FCE 24517) and epoxamido (FCE 24561) synthetic derivatives of distamycin A were reported in the present study. The 50% inhibiting concentration (IC50) of colony formation of FCE 24517 on human SNB-19 glioblastoma, A2780 ovarian cancer and DU 145 prostate cancer was at least three times lower than that of FCE 24561; on the same cell lines the IC50 of DXR was up to 14 and 240 times higher than that of FCE 24561 and FCE 24517, respectively. Isolated rat hearts perfused with concentrations of both derivatives equivalent to their respective IC50 values did not show any significant change in ECG parameters, contractility and coronary flow. Compared to control hearts, FCE 24517 10(-6) M induced a significant increase in PR interval, reduction in + dF/dtmax, heart rate and coronary flow, while FCE 24561 10(-6) M produced a modest but significant increase in S alpha T segment and decrease in + dF/dtmax. Rats treated with FCE 24561 3, 6 or 12 mg/kg, intravenously (i.v.), once weekly for 3 weeks had a modest increase in S alpha T segment and QRS complex duration, while a slight alteration of S alpha T segment and QRS complex duration were observed in rats given FCE 24517 1 or 2 mg/kg i.v. once weekly for 3 weeks. No cardiac histologic alterations were found in hearts from rats receiving FCE 24517 or FCE 24561. For comparison, the cardiotoxicity of doxorubicin (DXR) was evaluated in the same experimental models; perfusion of hearts with DXR 10(-6) M induced severe alterations in all parameters of the isolated hearts; the administration of DXR 3 mg/kg i.v. once a week for 3 weeks was associated with a widening of the S alpha T segment and QRS complex and cardiac histologic picture was markedly altered. In conclusion, distamycin A derivatives display elevated cytotoxicity while no substantial cardiotoxicity was observed.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Agen C,Sironi AM,Danesi R,Costa M,Bernardini N,Paparelli A,Della Torre P,Del Tacca Mdoi
10.1016/0300-483x(92)90003-wkeywords:
subject
Has Abstractpub_date
1992-11-15 00:00:00pages
209-19issue
3eissn
0300-483Xissn
1879-3185pii
0300-483X(92)90003-Wjournal_volume
75pub_type
杂志文章相关文献
TOXICOLOGY文献大全abstract::This paper introduces the special issue on quantitative in vitro-in vivo extrapolations (QIVIVE). It highlights important issues in the development of in vitro toxicology towards its implementation in toxicological risk assessment. ...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/j.tox.2014.04.004
更新日期:2015-06-05 00:00:00
abstract::Chronic ethanol intake affects various organ systems of the body. The present study evaluated modifications of fatty acid concentrations both in brain and striated skeletal muscles of rats genetically selected for voluntary high ethanol intake. Three groups of rats were tracked for 10 weeks of access to ethanol only a...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2004.02.023
更新日期:2004-07-01 00:00:00
abstract::Role of chromium(III) in biological systems is controversial and no significant conclusions can be arrived with the available data. Chromium(VI) enters in to the cell readily and gets reduced to form stable chromium(III) complexes. Chromium(III) complexes react slowly and were considered non-toxic. Recent studies sugg...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2008.07.052
更新日期:2008-09-29 00:00:00
abstract::Among exocyclic DNA adducts, etheno (epsilon) bases (epsilond A, epsilond C, N(2),3-epsilond G) are generated by reactions of DNA bases with lipid peroxidation (LPO) products derived from endogenous sources and from the carcinogens vinyl chloride or urethane. The recent development of ultrasensitive methods has made i...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/s0300-483x(00)00307-3
更新日期:2000-11-16 00:00:00
abstract::An experimental approach was taken to the question of dose-response curves for chemical carcinogenesis, using DNA damage as a biomarker. Female rats were give 13 different doses of 1,2-dimethylhydrazine (from 1.4 to 135,000 micrograms/kg) and the subsequent hepatic DNA damage was determined by the alkaline elution tec...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(96)03478-6
更新日期:1996-12-02 00:00:00
abstract::The present research examines the effects of 4-nonylphenol (4-NP) on mouse primary calvarial osteoblasts (COBs). Incubation of the cells with 4-NP at 10(-5)M and 10(-6)M striking decreased osteoblasts viability and phosphatidylserine (PS) exposure, measured by Annexin V, was greatly enhanced. In addition, an up-regula...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2011.10.014
更新日期:2011-12-18 00:00:00
abstract::Relative cytotoxicity and mechanism of action of thiophenes were investigated in suspensions of freshly isolated renal proximal tubular (PT) and distal tubular (DT) cells using 4-(2-thienyl)butyric acid (TByA) as a model compound. TByA produced significantly greater time- and concentration-dependent cytotoxicity, as a...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(95)03137-5
更新日期:1995-12-10 00:00:00
abstract::The usefulness of measuring serum bile acid concentrations by RIA in a number of acute experimental liver injuries of rats was assessed by comparing the concentrations with the results of some of the routinely employed methods of examining hepatotoxic changes. Centrilobular liver cell injury produced by CCl4 revealed ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(80)90005-0
更新日期:1980-01-01 00:00:00
abstract::Experiments were designed to evaluate and compare metallothionein (MT), zinc and cadmium levels in human placentas of smoking and non-smoking women. Smoking was assessed by self-reported cigarette consumption and urine cotinine levels before delivery. Smoking pregnant women with urine cotinine levels higher than 130 n...
journal_title:Toxicology
pub_type: 临床试验,杂志文章
doi:10.1016/j.tox.2004.11.016
更新日期:2005-03-01 00:00:00
abstract::This study compares changes in cardiopulmonary function, selected endpoints in exhaled breath, blood, and bronchoalveolar lavage fluid (BAL) following a single, high-level 30-min nose-only exposure of rats to chlorine and phosgene gas. The time-course of lung injury was systematically examined up to 1-day post-exposur...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2014.10.010
更新日期:2014-12-04 00:00:00
abstract::Food labels are an important educational tool to assist consumers in making healthy food choices. In addition to mandatory nutritional labeling information, manufacturers have a variety of options on the food/supplement packages to communicate the nutrition/health benefits of their products. This paper describes the d...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2005.12.021
更新日期:2006-04-03 00:00:00
abstract::Previous studies on the immunotoxicity of a complex mixture of polynuclear aromatic hydrocarbon (PAH) by-products from a manufactured gas plant indicated possible synergistic interactions which were investigated by determining the immunosuppressive effects of a reconstituted PAH mixture in female B6C3F1 mice challenge...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(95)03302-v
更新日期:1996-05-03 00:00:00
abstract::Mycotoxins (frequently referred to as secondary metabolites of toxigenic fungi) are commonly found in foodstuffs and are important because of their association with disease. The mycotoxin diacetoxyscirpenol, or 3-hydroxy-4,15-diacetoxy-12,13-epoxytrichothec-9-ene (DAS), is produced by numerous species of Fusarium and ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(87)90016-3
更新日期:1987-09-01 00:00:00
abstract::A single oral dose of 50 mg/kg of [14C]TOCP was administered in corn oil to male rats. Three animals were sacrificed at each of 2, 6 and 12 h and 1, 2 and 5 days following dosing, and tissues and excreta were analyzed for 14C. Within 5 days, 63 and 36% of the dose were recovered in the urine and feces, respectively. I...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(90)90079-v
更新日期:1990-12-17 00:00:00
abstract::Previous reports from this laboratory have established the propensity of chlordecone to potentiate the hepatotoxicity and lethality in male and female rats. The present study was designed to investigate the hepatotoxicity of CCl4 in chlordecone (CD) pretreated, ovariectomized rats. Ten days after bilateral ovariectomy...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(84)90163-x
更新日期:1984-02-01 00:00:00
abstract::Allyl acetate (AAC), allyl alcohol (AAL), and acrolein (ACR) are used in the manufacture of detergents, plastics, pharmaceuticals, and chemicals and as agricultural agents. A metabolic relationship exists between these chemicals in which allyl acetate is metabolized to allyl alcohol and subsequently to the highly reac...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2008.08.014
更新日期:2008-11-20 00:00:00
abstract::The cardiovascular toxin allylamine (3-aminopropene) has been shown to concentrate in elastic and muscular tissues. In this study the 14C-moiety of [14C]allylamine was traced in aortas of adult Sprague-Dawley rats after intravenously injecting 30 microCi of [14C]allylamine (spec. act. = 0.4 mCi/mM). At 5, 10, 15 and 2...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(85)90014-9
更新日期:1985-06-14 00:00:00
abstract::Recent Canadian research efforts have been directed towards the development of a reactive skin decontaminant (RSD) lotion active against classical nerve agents and mustard. The formulation presently under study consists of a 1.25 molal solution of potassium 2,3-butanedione monoximate (KBDO) in polyethylene glycol meth...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(91)90028-y
更新日期:1991-05-01 00:00:00
abstract::This paper presents an overview of issues related to surface water contamination arising from uranium mining activities in the Alligator Rivers Region (ARR) of northern Australia, and a program of research and monitoring that must assess the potential and actual effects on ecosystem and human health. The program of as...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/s0300-483x(02)00470-5
更新日期:2002-12-27 00:00:00
abstract::We have determined that the addition of 3-phenylamino-L-alanine (PAA), a recently reported contaminant in L-tryptophan implicated in the eosinophilia-myalgia syndrome, affects tryptophan binding by utilizing an in vitro measurement of 3H-tryptophan binding to hepatic nuclei or nuclear envelopes. PAA (10(-10) to 10(-4)...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(94)90058-2
更新日期:1994-01-26 00:00:00
abstract::We have previously shown that young guinea pigs repeatedly exposed to sidestream cigarette smoke (SS) develop decreased airway reactivity of the C-fiber system without changing reactivity to one of its neurotransmitters, substance P (SP). This study was designed to determine whether the decreased reactivity was due to...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(96)03403-8
更新日期:1996-09-02 00:00:00
abstract::Diesel exhaust particles (DEP) affect health adversely. Our previous studies revealed that DEP extracts up-regulated expression of genes related to drug metabolism, antioxidant enzymes, cell cycle/apoptosis and coagulation, and in addition, n-hexane soluble fraction (n-HSF) of DEP extracts contains aliphatic and polyc...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2009.05.012
更新日期:2009-07-28 00:00:00
abstract::In the clinical setting, antidotes are generally administered after the occurrence of a drug overdose. Therefore, the most pertinent evaluation of any new agent should model human exposure. This study tested whether acetaminophen (APAP) hepatotoxicity was reversed when S-adenosyl-L-methionine (SAMe) was administered a...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2007.10.027
更新日期:2008-02-03 00:00:00
abstract::Organotellurides are important intermediates in organic synthesis and, consequently, the occupational exposure to them is a constant risk for laboratory workers. These compounds can elicit many neurotoxic events in the central nervous system (CNS) that are associated with several neurological symptoms. In contrast, or...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2006.02.009
更新日期:2006-05-01 00:00:00
abstract::Trichloroethylene (TCE) produced bronchiolar damage when administered to mice. Administration of 2000 mg/kg caused injury in Clara cells of the bronchiolar epithelium, which was observed at 24 h following TCE treatment; increase of the dosage to 2500 mg/kg induced additionally, alterations in alveolar Type II cells of...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(85)90028-9
更新日期:1985-05-01 00:00:00
abstract::The effect of amyl nitrite on the erythrocytes of adult and cord hemoglobin was examined in vitro. This study revealed that amyl nitrite caused oxyhemoglobin to become oxidized to methemoglobin wherein a rectangular hyperbolic curve was generated as the reaction progressed. This curve consisted of a reactionary log ph...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(85)90003-4
更新日期:1985-07-01 00:00:00
abstract::Paracetamol, in toxic doses, is associated with extensive liver damage. This represents one of the common causes of morbidity and mortality in drug poisoning cases. This study was undertaken to investigate the possible potentiation of the hepatoprotective action of N-acetylcysteine (NAC) by cimetidine (CMD), an inhibi...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(97)00069-3
更新日期:1997-09-05 00:00:00
abstract::To evaluate hydroperoxide generation as a potential mechanism of cyanide neurotoxicity, mice were treated with KCN (7 mg/kg, subcutaneously (s.c.)) and the level of lipid peroxidation (expressed as conjugated dienes) was measured later in various organs. Brain showed elevated conjugated diene levels after cyanide but ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(94)90221-6
更新日期:1994-04-18 00:00:00
abstract::Cyclosporine (CsA) is a universally used immunosuppressive drug which induces adverse side effects in several organs, but its impact on the heart is still controversial. Small heat shock proteins (sHSPs), such as HSP25 and alpha B-crystallin, are cytoprotective stress proteins exceptionally represented in the heart. T...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2009.06.007
更新日期:2009-08-21 00:00:00
abstract::Rats were treated with a single dose of thallium acetate (32 mg/kg i.p.) and the antidotal effect of D-penicillamine and prussian blue given alone or in combination was assessed by means of evaluation of the thallium-induced cerebellar histological lesions. After thallium poisoning (24 h), antidotes were administered ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(94)90129-5
更新日期:1994-03-25 00:00:00