In vitro & molecular toxicology最新文献_第2页

Sedanolide, a natural phthalide from celery seed oil: effect on hydrogen peroxide and tert-butyl hydroperoxide-induced toxicity in HepG2 and CaCo-2 human cell lines. 芹菜籽油中的天然邻苯二甲酸:对过氧化氢和叔丁基过氧化氢诱导的HepG2和CaCo-2人细胞系毒性的影响。

In vitro & molecular toxicology Pub Date : 2001-01-01 DOI: 10.1089/109793301753407984

J. Woods, C. Jewell, N. O'Brien

{"title":"Sedanolide, a natural phthalide from celery seed oil: effect on hydrogen peroxide and tert-butyl hydroperoxide-induced toxicity in HepG2 and CaCo-2 human cell lines.","authors":"J. Woods, C. Jewell, N. O'Brien","doi":"10.1089/109793301753407984","DOIUrl":"https://doi.org/10.1089/109793301753407984","url":null,"abstract":"Sedanolide is a natural compound occurring in edible umbelliferous plants. Celery seed oil, a significant source of sedanolide, is used as an herbal remedy to treat inflammatory-associated conditions such as gout and rheumatism. The objective of this study was to assess the potential protective properties of sedanolide against hydrogen peroxide (H(2)O(2))- and tert-butyl hydroperoxide (tBOOH)-induced toxicity in HepG2 and CaCo-2 cells. Viability of HepG2 and CaCo-2 cells was unaffected by a 24-h exposure to sedanolide (7-500 microM), however, when the cells were cultured in sedanolide-free medium for a further two cell cycles (72 h), a decrease in cell viability was observed for HepG2 cells previously exposed to 500 microM of the compound. Cells pretreated with sedanolide (100 microM for 24 h) and exposed to either H(2)O(2) or tBOOH did not exhibit statistically significant difference in viability from controls. A significant increase (p < 0.05) in DNA strand breaks, as measured by the comet assay, was observed in HepG2 but not CaCo-2 cells following a 24-h incubation with 500 microM sedanolide. Sedanolide did not modulate H(2)O(2)- and tBOOH-induced DNA damage. Sedanolide is relatively nontoxic to cells in culture, however, the protection it afforded against H(2)O(2)- and tBOOH-induced toxicity was not statistically significant.","PeriodicalId":80284,"journal":{"name":"In vitro & molecular toxicology","volume":"14 3 1","pages":"233-40"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/109793301753407984","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60637070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 29

Trip report. 旅行报告。

In vitro & molecular toxicology Pub Date : 2001-01-01 DOI: 10.1089/10979330152560469

J. F. Sina

引用次数: 0

Metallothionein overexpression in human trophoblastic cells protects against cadmium-induced apoptosis. 金属硫蛋白在人滋养细胞中的过度表达对镉诱导的细胞凋亡具有保护作用。

In vitro & molecular toxicology Pub Date : 2001-01-01 DOI: 10.1089/109793301316882522

M. McAleer, R. Tuan

{"title":"Metallothionein overexpression in human trophoblastic cells protects against cadmium-induced apoptosis.","authors":"M. McAleer, R. Tuan","doi":"10.1089/109793301316882522","DOIUrl":"https://doi.org/10.1089/109793301316882522","url":null,"abstract":"Proper functioning of trophoblastic cells is essential for maintenance of the placenta and development of the embryo/fetus. Exposure of trophoblasts to toxic exogenous factors, such as cadmium (Cd), perturbs placental function and affects fetal outcome. Cellular responses to Cd exposure include induction of the metal-binding protein, metallothionein (MT), and initiation of apoptosis. To analyze the functional relationship between cellular MT levels and apoptosis in trophoblasts, we have examined the effects of DNA transfection-mediated alterations in MT levels on trophoblastic function and apoptosis, with and without Cd exposure, using the trophoblast-like JEG-3 human choriocarcinoma cell line. JEG-3 cells stably transfected with human MT-IIa cDNA expression constructs, in either sense or antisense orientation, were unchanged in human chorionic gonadotropin (hCG) production or expression of the apoptotic markers, bcl-2 and CPP-32. However, MT overexpression significantly prolonged the recovery time of intracellular Ca flux, whereas reduced basal MT increased the incidence of apoptosis as determined by morphology and terminal deoxynucleotidyl end labeling (TUNEL) staining. Upon Cd exposure, a dose-dependent decrease in hCG secretion was seen in all JEG-3 cultures, without any correlation to basal MT expression. Basal MT levels, however, significantly affected the extent of apoptosis, the incidence being inversely related to basal MT level. These results suggest that while MT does not ameliorate heavy-metal induced perturbation of some trophoblastic functions, its expression is critical for protection of these cells from Cd-induced apoptosis and could act to maintain placental integrity in cases of maternal Cd exposure.","PeriodicalId":80284,"journal":{"name":"In vitro & molecular toxicology","volume":"14 1 1","pages":"25-42"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/109793301316882522","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60635501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 38

Esterase inhibition in SH-SY5Y human neuroblastoma cells following exposure to organophosphorus compounds for 28 days. 暴露于有机磷化合物28天后SH-SY5Y人神经母细胞瘤细胞的酯酶抑制

In vitro & molecular toxicology Pub Date : 2001-01-01 DOI: 10.1089/10979330152560522

D. Barber, M. Ehrich

{"title":"Esterase inhibition in SH-SY5Y human neuroblastoma cells following exposure to organophosphorus compounds for 28 days.","authors":"D. Barber, M. Ehrich","doi":"10.1089/10979330152560522","DOIUrl":"https://doi.org/10.1089/10979330152560522","url":null,"abstract":"Esterase inhibition was determined in SH-SY5Y human neuroblastoma cells grown in serum-free media and exposed to 10(-11) to 10(-7) M concentrations of organophosphorus (OP) compounds for 28 days. To examine metabolic activation in these exposures, pairs of pro- and active toxicants were studied, including chlorpyrifos and its oxon, parathion and paraoxon, and tri-ortho-tolyl phosphate and phenyl saligenin phospahte. Inhibition of acetylcholinesterase was greater in cells treated for 28 days with all active organophosphorus compounds than it was in cells treated only once with the same concentration of a given OP compound. The protoxicants chlorpyrifos and parathion produced acetylcholinesterase inhibition after multiple exposures although no inhibition was seen following a single exposure to these agents. Exacerbation of neurotoxic esterase inhibition by multiple exposures to the test compounds was not as pronounced as that of acetylcholinesterase. Exposure to the test compounds for 28 days did not significantly enhance esterase inhibition produced by a subsequent exposure to 10(-9) M chlorpyrifos-oxon. The results indicate that in vitro methods can be used to study the effect of multiple OP exposures on esterase activity.","PeriodicalId":80284,"journal":{"name":"In vitro & molecular toxicology","volume":"14 2 1","pages":"129-35"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/10979330152560522","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60635938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

Selective loss of viability of mouse NK cells in culture is associated with decreased NK cell lytic function. 小鼠NK细胞在培养中选择性丧失活力与NK细胞溶解功能下降有关。

In vitro & molecular toxicology Pub Date : 2001-01-01 DOI: 10.1089/10979330152560478

P. Hébert, S. Pruett

{"title":"Selective loss of viability of mouse NK cells in culture is associated with decreased NK cell lytic function.","authors":"P. Hébert, S. Pruett","doi":"10.1089/10979330152560478","DOIUrl":"https://doi.org/10.1089/10979330152560478","url":null,"abstract":"Cell culture methods can allow investigation of the mechanisms responsible for immunotoxicity. Unfortunately, natural killer (NK) cells in rodent splenic cultures rapidly lose their cytolytic function. It is not known if death of NK cells or loss of function in viable NK cells is primarily responsible for this loss. Flow cytometry and an assay of NK cell lytic function were used to address this issue and to determine if NK cell viability could be maintained by adding selected cytokines or a caspase inhibitor to the cultures. Total cells and NK cells in untreated 18 h cultures were 79 +/- 1% and 25 +/- 2% viable, respectively, and these cultured splenocytes caused only 4 +/- 1% specific release of (51)Cr from YAC-1 target cells. Cultures including polyinosinic:polycytidylic acid (poly I:C) or IL-2 had increased NK cell viability (43 +/- 2%, 47 +/- 1%) and function (58 +/- 2 and 43 +/- 1% specific release). IL-15 significantly increased NK cell viability, but not function. Previous studies demonstrated that treatment of mice with immunotoxicants such as ethanol or corticosterone diminishes NK cell activation in vitro in response to poly I:C. To determine if alterations in viability are responsible for this decreased NK cell activity, lytic function and NK activity were measured in cultures of splenocytes treated in vivo or in vitro with ethanol and/or corticosterone. Some treatments reduced IL-2 or poly I:C-enhanced lytic activity in vitro, but there was no clear relationship between these changes in function and changes in the percentage of viable NK cells. Thus, immunotoxicants that suppress NK cell activation can be investigated in vitro because commonly used activating stimuli also permit NK cell survival. However, no agents were identified that could maintain NK cell viability and function in culture (without activation) to allow investigation of the direct effects of immunotoxicants on basal NK activity in vitro.","PeriodicalId":80284,"journal":{"name":"In vitro & molecular toxicology","volume":"14 2 1","pages":"71-82"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/10979330152560478","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60635982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

Morphological transformation of Syrian hamster embryo cells at pH 6.7 by bemitradine, a nongenotoxic carcinogen. 非基因毒性致癌物贝米特拉定对pH为6.7的叙利亚仓鼠胚胎细胞形态的影响。

In vitro & molecular toxicology Pub Date : 2001-01-01 DOI: 10.1089/10979330152560513

Y. Oshiro, P. Balwierz, D. Morris, C. Alden, R. T. Bunch

{"title":"Morphological transformation of Syrian hamster embryo cells at pH 6.7 by bemitradine, a nongenotoxic carcinogen.","authors":"Y. Oshiro, P. Balwierz, D. Morris, C. Alden, R. T. Bunch","doi":"10.1089/10979330152560513","DOIUrl":"https://doi.org/10.1089/10979330152560513","url":null,"abstract":"Bemitradine is a compound that was intended for use as a diuretic antihypertensive drug. In the preclinical safety assays, it was found to be nongenotoxic in five in vitro assays (Ames, mouse lymphoma, CHO/HGPRT, CHO chromosome aberration, and UDS) and in one in vivo assay (mouse bone marrow micronucleus). In a subsequent long-term bioassay using Sprague-Dawley rats, this compound was found to be a rodent carcinogen at multiple sites. Because of the carcinogenicity, further development of this compound as a drug was halted. Because the Syrian hamster embryo (SHE) cell transformation assay at pH 6.7 has been demonstrated to be a good predictor of carcinogenic activity in animals, this nongenotoxic compound was used to determine if this in vitro assay system could be utilized to predict the potential for the carcinogenicity in rodents. The SHE cell transformation assay was validated initially for use in this laboratory using genotoxic and nongenotoxic carcinogens including benzo(a)pyrene, 20-methylcholanthrene, 2-acetylaminofluorene, methapyrilene, and phenobarbital. Each of these chemicals induced a statistically significant increase in morphological transformation frequency. Bemitradine was initially tested in a range-finding cytotoxicity assay at 10-250 microg/mL for treatment periods of 7 days. Doses used in the 7-day treatment transformation assay were 1.25, 2.5, 5.0, 7.5, and 10.0 microg/mL. Statistically significant increases in morphological transformation frequencies were observed at 1.25, 2.5, and 7.5 microg/mL, indicating a positive response. The experiment was repeated with similar results confirming the previous conclusion. These data provide additional evidence that the pH 6.7 SHE cell transformation assay may be a valuable in vitro tool to detect nongenotoxic rodent carcinogens.","PeriodicalId":80284,"journal":{"name":"In vitro & molecular toxicology","volume":"14 2 1","pages":"121-7"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/10979330152560513","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60635754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Effects of differently oxidized LDL on the expression of pro-inflammatory molecules in human monocytes in vitro. 不同氧化LDL对体外人单核细胞促炎分子表达的影响。

In vitro & molecular toxicology Pub Date : 2001-01-01 DOI: 10.1089/10979330152560487

Ruta Dominaitiene, Stefan Lindgren, Sabina Janciauskiene

{"title":"Effects of differently oxidized LDL on the expression of pro-inflammatory molecules in human monocytes in vitro.","authors":"Ruta Dominaitiene, Stefan Lindgren, Sabina Janciauskiene","doi":"10.1089/10979330152560487","DOIUrl":"https://doi.org/10.1089/10979330152560487","url":null,"abstract":"The oxidation of low-density lipoprotein (LDL) is thought to be a major contributor to the development of atherosclerosis and considerable evidence has accumulated showing that oxidized LDL (ox LDL) induces cell damage and pro-atherogenic events. However, evidence that oxidized LDL directly causes atherosclerosis is lacking. We studied whether native and enzymatically or chemically ox LDL at concentrations of 5 and 100 microg/mL is cytotoxic to or promotes pro-atherogenic activation of human primary monocytes in culture. Both types of ox LDL (100 microg/mL), but not native LDL added to monocytes for 24 h significantly diminish DNA synthesis and increase cell death. In addition, both preparations of ox LDL inhibit cytokine and metalloproteinase production, diminish cellular oxygen consumption and induce PPAR gamma expression. Enzymatically ox LDL, but not LDL oxidized by copper sulfate, also increases the monocyte metabolic rate and induces intracellular lipid accumulation. Low concentrations of either preparation of oxidized and native LDL did not show significant effects on all parameters measured. These data establish a direct link between ox LDL concentration and cytotoxicity and suggest that oxidation by copper of the lipid moiety in LDL and of the protein moiety by enzyme creates ox LDL, which can damage monocytes without release of pro-inflammatory molecular species. In contrast to native and enzymatically ox LDL, copper ox LDL does not induce intracellular lipid accumulation. Differently oxidized LDL molecules may exert distinct effects in lesion development in atherosclerosis.","PeriodicalId":80284,"journal":{"name":"In vitro & molecular toxicology","volume":"14 2 1","pages":"83-97"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/10979330152560487","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60636036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Bisphenol a binds to the low-affinity estrogen binding site. 双酚a与低亲和力雌激素结合位点结合。

In vitro & molecular toxicology Pub Date : 2001-01-01 DOI: 10.1089/109793301316882531

W. Washington, L. Hubert, D. Jones, W. Gray

{"title":"Bisphenol a binds to the low-affinity estrogen binding site.","authors":"W. Washington, L. Hubert, D. Jones, W. Gray","doi":"10.1089/109793301316882531","DOIUrl":"https://doi.org/10.1089/109793301316882531","url":null,"abstract":"Environmental estrogens are suspected of being involved in the current increase in the incidence of human reproductive malfunctions, such as a decrease in male reproductive capacity and an increased incidence of breast cancer in women. The influences of these compounds have been proposed to be mediated through binding to macromolecules, such as estrogen receptor alpha or beta. In this study we examined whether the low-affinity Type II estrogen binding site (Type II EBS), originally identified in the rat uterus, is a possible mediator of environmental estrogens such as bisphenol A (BPA). Analysis of BPA's binding to an enriched fraction of Type II EBS, using a competition assay, indicated that BPA was able to compete with estradiol in binding to this site. At a concentration of 10-15 microM (comparable to that required to induce uterine proliferation), BPA inhibited the binding of estradiol to Type II EBS by greater than 50%. The binding affinity of BPA for the Type II EBS was only 8-10-fold lower than that of the synthetic estrogen diethylstilbestrol. The binding of BPA to Type II EBS appeared specific to BPA, in that endosulfan, another environmental estrogen, failed to displace estradiol from the site. A comparison of the relative binding affinities of BPA for rat uterine estrogen receptor alpha to that of the Type II EBS implies that BPA preferentially binds to the Type II EBS.","PeriodicalId":80284,"journal":{"name":"In vitro & molecular toxicology","volume":"14 1 1","pages":"43-51"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/109793301316882531","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60635183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 31

Prediction models for eye irritation potential based on endpoints of the HETCAM and neutral red uptake tests. 基于HETCAM和中性红色摄取试验终点的眼睛刺激电位预测模型。

In vitro & molecular toxicology Pub Date : 2001-01-01 DOI: 10.1089/109793301753407911

Andrew Paul Worth, M. Cronin

引用次数: 14

Ultrastructural and histological effects of exposure to CEES or heat in a human epidermal model. 暴露于CEES或热对人体表皮模型的超微结构和组织学影响。

In vitro & molecular toxicology Pub Date : 2001-01-01 DOI: 10.1089/109793301316882513

M. Blaha, J. Kohl, D. Dubose, W. Bowers, J. Walker

{"title":"Ultrastructural and histological effects of exposure to CEES or heat in a human epidermal model.","authors":"M. Blaha, J. Kohl, D. Dubose, W. Bowers, J. Walker","doi":"10.1089/109793301316882513","DOIUrl":"https://doi.org/10.1089/109793301316882513","url":null,"abstract":"Ultrastructural and terminal deoxynucleotidyl transferase nick end labeling (TUNEL) studies were conducted to compare mechanisms of 2-chloroethyl ethyl sulfide (CEES) and heat-induced injury to EpiDerm. Twenty-two hours after 2-h exposure to the monofunctional alkylating agent CEES, budding of cytoplasm, clumping of nuclear chromatin, disintegration of nuclear membranes and cytoplasmic structures, and cytoplasmic vacuolization were detected, especially in the basal cells near the pseudobasement membrane. TUNEL techniques revealed DNA fragmentation distinct from that normally associated with terminal keratinocyte differentiation. Similar evaluations 22.5 h after 90 min exposure of EpiDerm to elevated temperature (45 degrees C) produced a different pattern of cell damage. Swelling of intercellular spaces, extensive cytoplasmic vacuolization, disruption of normal nuclear shape, reduced cell membrane integrity, and release of cellular material in the basal region characterized heat injury. Heat did not alter the DNA fragmentation normally associated with keratinocyte maturation. These data suggest that CEES elicited an apoptotic mechanism of cell death with features of terminal differentiation such as nuclear membrane disintegration and loss of cytoplasmic structures. Heat, alternatively, produced changes more typical of oncotic necrosis.","PeriodicalId":80284,"journal":{"name":"In vitro & molecular toxicology","volume":"14 1 1","pages":"15-23"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/109793301316882513","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60635375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11