Abstract:
:Transgenic rodents that contain easily retrievable target genes allow the rapid quantitation of mutations in any tissue from which DNA can be isolated. We are using the Stratagene Big Blue transgenic mouse system that contains a lacI target and an alpha lacZ reporter gene to study the parameters that affect mutations. We have evaluated a number of chemicals to determine mutant frequency (MF) in specific target tissues of C57Bl/6 and B6C3F1 mice. The correlation between mutagenesis and carcinogenesis in this system is excellent. For example, the liver carcinogen dimethylnitrosamine produces significant increases in MF in mouse liver, whereas the nonhepatocarcinogenic mutagen methylmethane sulfonate does not. We have also evaluated the induction of mutations by radiation and demonstrated that this system is suitable for the study of agents that produce deletion mutations. This system is also useful for studying changes in MF in developing tumors. We have used an initiation-promotion protocol to induce hepatocellular carcinomas, and we then measured MF in normal liver, tumors, and metastases from these mice. Animals initiated with diethylnitrosamine maintain an elevated MF in normal liver, even 1 year after initiation. This MF increases exponentially in developing liver tumors, possibly owing to a breakdown in the fidelity of DNA replication and DNA repair in tumors. This system offers a unique tool for the study of mutations induced in specific target tissues of rodents and should become an important assay for evaluating the mutagenic risk of drugs and chemicals.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Mirsalis JCdoi
10.1016/0378-4274(95)03472-2subject
Has Abstractpub_date
1995-12-01 00:00:00pages
131-4eissn
0378-4274issn
1879-3169pii
0378-4274(95)03472-2journal_volume
82-83pub_type
杂志文章,评审abstract::Amitriptyline hydrochloride, an antidepressant drug, was tested in mice for mutagenic effects in the somatic cells by the micronucleus test and in the germ cells by the air drying technique of Evans et al. Mice were treated orally with the drug at a dose of 70, 140 and 210 mg/kg body weight. The results indicate that ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(87)90233-5
更新日期:1987-12-01 00:00:00
abstract::Cadmium (Cd), is a well-known environmental and occupational hazard with a potent neurotoxic action. However, the mechanism underlying cadmium-induced neurotoxicity remains unclear. Herein, we exposed Neuro-2a cells to different concentrations of cadmium chloride (CdCl2) (12.5, 25 and 50 μM) for 24 h and found that Cd...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2018.07.015
更新日期:2018-10-01 00:00:00
abstract::Nephrotoxicity limits the therapeutic efficacy of the antineoplastic drug cisplatin. Due to dosage adjustment and appropriate monitoring, most therapeutic courses with cisplatin produce no or minimal kidney damage. However, we studied whether even sub-nephrotoxic dosage of cisplatin poses a potential risk for the kidn...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2014.11.033
更新日期:2015-04-16 00:00:00
abstract::This study was conducted to evaluate whether vitamin C (VC) was associated with total antioxidant status (TAS) in human plasma and to determine the usefulness of VC on TAS in the treatment of patients with paraquat poisoning. VC and TAS were measured in 56 healthy subjects. Then, various concentrations (1-100 mg/dl) o...
journal_title:Toxicology letters
pub_type: 临床试验,杂志文章
doi:10.1016/s0378-4274(01)00431-3
更新日期:2002-01-05 00:00:00
abstract::Cadmium-binding proteins (CdBPs) in the cytosol fractions from several organs of man orally exposed to cadmium (Cd) were examined by gel chromatography. In kidney and liver most of the cadmium (76-87%) in the cytosols was bound to metallothionein, and hepatic metallothionein contained zinc also at a similar level. The...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(82)90160-6
更新日期:1982-05-01 00:00:00
abstract::New metabolites of styrene, three isomeric vinylphenylmercapturic acids (2-, 3-, and 4-VPMA), were recently identified by LC-ESI-MS in the urine of mice. In this study, 4-VPMA together with traces of 2- and 3-VPMA were found also in the urine of hand-lamination workers, which were exposed to styrene vapours at concent...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2012.06.012
更新日期:2012-09-03 00:00:00
abstract::Tubule segments from defined stages of the mouse seminiferous epithelium were incubated for 4, 8 and 24 h in the presence of different concentrations of mono-2-ethylhexyl phthalate (MEHP), adriamycin, and N-ethyl-N-nitrosourea (ENU) to study the effects of these chemicals on germ cell apoptosis and DNA synthesis. Apop...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(03)00170-x
更新日期:2003-07-20 00:00:00
abstract::An overview of values for the threshold of toxicological concern (TTC) is presented. This comprises the more established TTC values, including those that have been endorsed by regulatory bodies, and those that have more recently been proposed and may still need further development. The overview is structured by use/ex...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/j.toxlet.2012.03.795
更新日期:2012-06-20 00:00:00
abstract::Information about the effects of phytoestrogens in the liver, the main organ of metabolism, is limited. In this study we have examined the dose dependent effects of the phytoestrogen genistein (GEN) on gene expression in rat liver in comparison to the potent estrogen ethinylestradiol (EE). Special attention was paid t...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2005.01.001
更新日期:2005-05-16 00:00:00
abstract::The oral LD50 of hymenoxon in Swiss white mice was found to be 241 +/- 37 mg/kg. No significant sex differences were observed. Pretreatment of male mice for 3 days using doses of 50 and 100 mg/kg hymenoxon failed to alter significantly pentobarbital sleeping time. Hymenoxon was found to be a direct-acting mutagen in t...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(81)90016-3
更新日期:1981-12-01 00:00:00
abstract::Tetramethylenedisulfotetramine (TMDT) is a synthetic neurotoxic rodenticide and potential chemical threat agent. Signs of TMDT poisoning include convulsions which can progress into status epilepticus and death. Although clinical reports clearly show that poisoning via food and drink is the main route of exposure, expe...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2019.03.014
更新日期:2019-06-15 00:00:00
abstract::Due to the massive reduction of air-change rates in modern, energy-saving houses and dwellings, the contribution of volatile organic compound (VOCs) emissions from wood-based materials to indoor air quality has become increasingly important. To evaluate toxicity of VOC mixtures typically emitted from pine wood and ori...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2010.03.015
更新日期:2010-06-16 00:00:00
abstract::On chronic administration of 20 microliter of chilli extract to the cheek pouch of hamsters till death, 23% of the hamsters developed shrunken eye balls and closing of the eyelids. This effect was not observed in hamsters which received a single application of the potent carcinogen methylacetoxymethyl nitrosamine (DMN...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(85)90002-5
更新日期:1985-10-01 00:00:00
abstract::The effects of cytochrome P-450 inhibition by alpha-phenyl-alpha-propylbenzeneacetic acid 2-[diethylamino]-ethyl ester hydrochloride (SKF-525A), which inhibits the activity of a number of cytochrome P-450s, on triphenyltin metabolism and toxicity in mice were studied. At 24 h after triphenyltin administration, the tri...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(00)00255-1
更新日期:2000-11-20 00:00:00
abstract::Paraquat poisoning results in damages of multiple organs including liver, kidney and lung, and antioxidants have been proven to have protective effects. As a novel free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), was introduced to clinical use recently, its protective effect was studied on acute ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(03)00113-9
更新日期:2003-06-05 00:00:00
abstract::Work with sub-natural levels of deuterium (D) in animals has demonstrated an anti-cancer effect of low D-concentration in water. Our objective was to investigate whether deuterium-depleted water (DDW) can overturn reverse manganese (Mn)-induced reduction in life span, using the Caenorhabditis elegans (C. elegans) as a...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2012.04.014
更新日期:2012-06-20 00:00:00
abstract::The effect of a single i.p. injection of 0, 20, 200, and 1000 microliter/kg carbon tetrachloride on the activity of the hepatic drug-metabolizing enzyme system was measured in the rat by a model substrate assay employing lindane (gamma-hexachlorocyclohexane) and by a battery of in vitro enzyme assays. The data in this...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(88)90116-6
更新日期:1988-09-01 00:00:00
abstract::In present study, we compared for the first time the cytotoxicities of the 16 priority polycyclic aromatic hydrocarbons (PAHs) in human pulmonary alveolar epithelial cells HPAEpiC. Moreover, we examined the effects of each PAH on oxidative stress (SOD, GSH, and ROS), cell viability, extracellular LDH, and apoptosis. T...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2018.03.005
更新日期:2018-06-15 00:00:00
abstract::Voltage-activated sodium channels and GABAA receptor-chloride channel complex are among the most important target sites of various environmental neurotoxicants. Pyrethroids keep the sodium channels open for prolonged periods of time leading to hyperexcitation of the entire nervous system. In rat cerebellar Purkinje ne...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/0378-4274(95)03482-x
更新日期:1995-12-01 00:00:00
abstract::The incidence of spontaneous neoplasms in outbred, inbred and F1 hybrid strains was compared using the Charles River-CD rat and mouse, the F344 rat, and B6C3HF1 mouse. These strains are commonly used in carcinogenic studies. Each strain has a consistent pattern of tumor occurrence; testicular, pituitary and lymphoreti...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(82)90113-8
更新日期:1982-04-01 00:00:00
abstract::Mercury(II) ions are known to accumulate in the kidney and their effect upon the renin-angiotensin system has also been described. The question, however, whether mercury(II) also exerts direct effect on the juxtaglomerular cells (JGC) to induce renin release remained to be answered. Suspension of isolated glomeruli wa...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(96)03637-5
更新日期:1996-04-01 00:00:00
abstract::The relative toxicity of three legacy and six emerging brominated flame retardants* was studied in the male Harlan Sprague Dawley rat. The hepatocellular and thyroid toxicity of each flame retardant was evaluated following five-day exposure to each of the nine flame retardants (oral gavage in corn oil) at 0.1-1000 μmo...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2020.07.016
更新日期:2020-10-10 00:00:00
abstract::Metallothionein (MT) is inducible by various stimuli such as metals and physiological stress. Although elevated MT expression in certain type of tumors has been reported, there are few data available on the roles of MT in tumor formation. In this study, we immunohistochemically examined MT expression in gluthathione S...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(99)00127-7
更新日期:1999-07-30 00:00:00
abstract::Intraperitoneal (i.p.) and intravenous (i.v.) injection of 44Ti in a chloride solution into mice produced no detectable translocation in body fluids. There was no obvious interorgan exchange up to 16 days after injection. The whole body biological retention half-lives had a mean of 642 days for both routes, another in...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(80)90177-0
更新日期:1980-07-01 00:00:00
abstract::Environmental exposure to the highly persistent chlorinated pesticides including dieldrin and lindane is postulated to be a risk factor to the development of Parkinson's disease, a devastating movement disorder. We have previously reported that the combined treatment with dieldrin and lindane induces a cooperative tox...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2018.09.006
更新日期:2018-12-15 00:00:00
abstract::There are numerous observations of pharmaceuticals (or their metabolites) as contaminants in wastewater, surface water and groundwater. This implies a potential for indirect human exposure to pharmaceuticals via drinking water supplies. Various effect benchmarks may be employed in an evaluation of the significance of ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(03)00071-7
更新日期:2003-05-15 00:00:00
abstract::Cholestasis represents pathophysiologic syndromes defined as impaired bile flow from the liver. As an outcome, bile acids accumulate and promote hepatocyte injury, followed by liver cirrhosis and liver failure. Glycochenodeoxycholic acid (GCDCA) is relatively toxic and highly concentrated in bile and serum after chole...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2020.05.017
更新日期:2020-10-01 00:00:00
abstract::Mutagenic activity of aflatoxin B1 (AFB1) was followed in the Ames Salmonella/microsome test using liver S-9 from control and partially hepatectomized (PH) mice. The S-9 preparations from the PH mice were capable of inducing significantly greater AFB1 mutagenic activity to strain TA100 than S-9 preparations from eithe...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(82)90060-1
更新日期:1982-12-01 00:00:00
abstract::We have previously shown that rituximab has a significant radiosensitizing effect on Raji cells in vitro. To investigate whether calcium signals participate in rituximab- and radiation-induced cell death in Raji cells, confocal laser scanning microscopy was used to detect kinetic changes in intracellular free calcium ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2011.12.018
更新日期:2012-03-25 00:00:00
abstract::The effect of aflatoxin B1 on the uptake and incorporation of [3H]leucine and [3H]uridine and on phagocytosis of latex particles was studied using cultures of rat liver macrophages (Kuffer cells). Aflatoxin B1 inhibited the incorporation of both isotopes, but inhibition of uridine incorporation was greater than that o...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(85)90039-6
更新日期:1985-12-01 00:00:00