Molecular toxicology最新文献_第7页

Macrophage functional activities versus cellular parameters upon sublethal pesticide exposure in mice. 亚致死农药暴露后小鼠巨噬细胞功能活性与细胞参数的关系。

Molecular toxicology Pub Date : 1987-04-01

K Krzystyniak, B Trottier, P Jolicoeur, M Fournier

{"title":"Macrophage functional activities versus cellular parameters upon sublethal pesticide exposure in mice.","authors":"K Krzystyniak, B Trottier, P Jolicoeur, M Fournier","doi":"","DOIUrl":"","url":null,"abstract":"The toxicity of selected organochlorine, organophosphate, and carbamate pesticides on the functions and cellular parameters of peritoneal macrophages was examined in inbred C57Bl/6 mice. Effects of single, sublethal pesticide exposure on macrophages were determined by analysis of the cell viability, cell adherence capacity, generation of superoxide anion (O2-), antigen processing, phagocytosis of Salmonella typhimurium, and resistance to in vitro virus-induced cytopathic effects (cpe) after infection with mouse hepatitis virus 3 (MHV3). Most of the studies were done for the organochlorine pesticide dieldrin, which inhibited several macrophage functions, such as phagocytosis of S. typhimurium, release of the single processed protein antigen avidin, and resistance to MHV3 virus-induced cpe. The virus-induced cytolysis in macrophage cultures was significantly increased after in vivo exposure to single sublethal doses of other selected pesticides, such as guthion, carbofuran, sevin, and matacil. However, none of the selected pesticides, used in sublethal (0.4 less than or equal to LD50 less than or equal to 0.6) doses appeared to be a factor impairing the O2- -generating system in chemically elicited or immunologically activated peritoneal macrophages. In conclusion, sublethal pesticide exposure can induce a significant impairement of several macrophage functions, such as phagocytosis, antigen processing, and resistance to virus-induced cytolysis. Inhibition of the O2- -generating system by sublethal pesticide exposure, however, can be excluded as a mechanism of potential suppressory action of these pesticides on antiviral and antibacterial host defence systems in which macrophages play a primary role.","PeriodicalId":77750,"journal":{"name":"Molecular toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13973936","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: 0

Differing effects of chronic ethanol consumption by mice on liver microsomal metabolism of xenobiotics: 1-nitropyrene, nicotine, aniline, and N-nitrosopyrrolidine. 慢性乙醇消耗对小鼠肝微粒体代谢的不同影响:1-硝基芘、尼古丁、苯胺和n -亚硝基吡咯烷。

Molecular toxicology Pub Date : 1987-04-01

P C Howard, G J DeMarco, M C Consolo, G D McCoy

引用次数: 0

Natural cytotoxins in human plasma: isolation and characterization of phospholipids associated with cytotoxic lipoproteins. 人血浆中的天然细胞毒素:与细胞毒性脂蛋白相关的磷脂的分离和表征。

Molecular toxicology Pub Date : 1987-04-01

J A Prezioso, P H Koo

引用次数: 0

Analysis of the molecular electrostatic potential for the prediction of N-oxidation and biological activity of substituted pyridines. 分子静电势分析预测取代吡啶的n -氧化和生物活性。

Molecular toxicology Pub Date : 1987-04-01

K Namboodiri, R Osman, H Weinstein, J R Rabinowitz

{"title":"Analysis of the molecular electrostatic potential for the prediction of N-oxidation and biological activity of substituted pyridines.","authors":"K Namboodiri, R Osman, H Weinstein, J R Rabinowitz","doi":"","DOIUrl":"","url":null,"abstract":"Comparative studies on the reactivity of the heterocyclic nitrogen were carried out for pyridine and its three monosubstituted derivatives 2-aminopyridine (2-AP), 3-aminopyridine (3-AP), and 4-aminopyridine (4-AP) to reveal the structural basis for the differences in their susceptibility to N-oxidation. Molecular orbital calculations were performed to obtain the wave functions for the calculation of the molecular electrostatic potentials (MEP) generated by the molecules. The comparison of the reactivity of the cyclic nitrogen, evaluated from the depth and accessibility of the minimum in the MEP, indicates that the nitrogen in 4-AP will be most susceptible to protonation and will be the most protected from N-oxidation at physiological pH values. The MEP map for 2-AP reveals the smallest minimum in the series of compounds and a considerable reduction in the accessibility of the region near the cyclic nitrogen caused by the proximal substitution. On this basis, 3-AP becomes the most likely derivative to form the ring N-oxide. Comparison of the conclusions from the MEP analysis with available data from bioassays suggests that the mechanism responsible for the genotoxic effects of the chemicals, where only 3-AP is active, is very different from the mechanism for systemic toxicity where 3-AP is the least active, and 4-AP is most active probably due to its channel blocking properties. As the mechanisms for the biological activities of the N-oxide metabolites become clear, reliable predictions of the toxicity of the pyridines should become possible based on such reactivity characteristics.","PeriodicalId":77750,"journal":{"name":"Molecular toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14574465","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: 0

Interaction of aflatoxin B1 and cyclopiazonic acid toxicities. 黄曲霉毒素B1与环吡唑酸毒性的相互作用。

Molecular toxicology Pub Date : 1987-01-01

I E Yates, R J Cole, J L Giles, J W Dorner

引用次数: 0

Inhibition of gap junctional-mediated intercellular communication in vitro by aldrin, dieldrin, and toxaphene: a possible cellular mechanism for their tumor-promoting and neurotoxic effects. 艾氏剂、狄氏剂和毒杀芬对间隙连接介导的细胞间通讯的体外抑制:其促肿瘤和神经毒性作用的可能细胞机制。

Molecular toxicology Pub Date : 1987-01-01

J E Trosko, C Jone, C C Chang

引用次数: 0

Nitrosamine carcinogen activation pathway determined by quantum chemical methods. 量子化学方法确定亚硝胺致癌物激活途径。

Molecular toxicology Pub Date : 1987-01-01

M Poulsen, D Spangler, G H Loew

{"title":"Nitrosamine carcinogen activation pathway determined by quantum chemical methods.","authors":"M Poulsen, D Spangler, G H Loew","doi":"","DOIUrl":"","url":null,"abstract":"Multiple reactions are thought to be involved in transforming dialkynitrosamines to active carcinogens. The first proposed step is enzymatic alpha-hydroxylation by the active oxygen species of cytochrome P-450, followed by nonenzymatic N-dealkylation and formation of diazohydroxides (RNNOH). The latter transformation can reasonably occur by a two-step mechanism via tautomerization of a monoalkylnitrosamine intermediate or directly from the alpha-hydroxylated species in one step. Both of these pathways in the transformation of hydroxymethylnitrosamine to diazohydroxide and formaldehyde were examined by the semiempirical molecular orbital method MNDO (modified neglect of diatomic differential overlap) and the ab initio method using STO-3G and 3-21G basis sets. Complete geometry optimizations of all reactants, intermediates, transition states, and products were performed. MNDO was also used to compare the similar transformation of the dimethyl analog. Both methods show that in the gas phase a concerted pathway involving a six-membered ring transition-state pathway is kinetically favored over a two-step pathway involving N-demethylation followed by tautomerization via two four-membered ring transition states. This reaction appears to be a viable one to formation of an ultimate carcinogen by parent dialkylnitrosamines in the hydrophobic substrate binding site of cytochrome P-450.","PeriodicalId":77750,"journal":{"name":"Molecular toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14574464","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: 0

beta,beta'-Iminodipropionitrile (IDPN) neurotoxicity: a mechanistic hypothesis for toxic activation. -亚氨基二丙腈(IDPN)神经毒性:毒性激活的机制假说。

Molecular toxicology Pub Date : 1987-01-01

A R Jacobson, S H Coffin, C M Shearson, L M Sayre

{"title":"beta,beta'-Iminodipropionitrile (IDPN) neurotoxicity: a mechanistic hypothesis for toxic activation.","authors":"A R Jacobson, S H Coffin, C M Shearson, L M Sayre","doi":"","DOIUrl":"","url":null,"abstract":"beta,beta'-Iminodipropionitrile (IDPN) induces neurobehavioral aberrations in experimental animals and massive focal accumulations of neurofilaments in proximal regions of axons. A hypothesis is presented to explain the neurotoxic activity of IDPN in terms of oxidative amine metabolism, wherein a resonance-stabilized cyanoenamine 3-(2-cyanoethylamino)acrylonitrile (dehydro-IDPN, 5) could be generated. Chemical studies were conducted to verify the likelihood of the proposed enzymatic transformations and their consistency with the known excreted metabolites. Dehydro-IDPN gives rise to a slow hydrolytic release of cyanoacetaldehyde at pH 7, which can transform protein-based amino groups to cyanoenamines, though the latter derivatives could be formed directly through a relatively rapid transamination reaction with dehydro-IDPN at pH 7. Kinetic studies were conducted to assess the balance between competing hydrolysis (pseudo-first order) and transamination (second order) of cyanoenamines as a function of pH. Cyanoethenylation of the epsilon-amino groups of critical lysine residues in the \"tail-piece\" domains of neurofilament (NF) subunit proteins could disrupt the supramolecular coulombic interactions thought to contribute to maintenance of cytoskeletal caliber. This could result in a defect in the slow axonal transport of NF, and subsequently in the formation of proximal axonal enlargements.","PeriodicalId":77750,"journal":{"name":"Molecular toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14574463","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: 0

Carcinogenicity prediction and battery selection procedure: an in-depth analysis of cyclamate and its major metabolite cyclohexylamine. 致癌性预测和电池选择程序:深入分析环己胺及其主要代谢物环己胺。

Molecular toxicology Pub Date : 1987-01-01

Y Y Haimes, V Chankong, J Pet-Edwards, H R Rosenkranz

{"title":"Carcinogenicity prediction and battery selection procedure: an in-depth analysis of cyclamate and its major metabolite cyclohexylamine.","authors":"Y Y Haimes, V Chankong, J Pet-Edwards, H R Rosenkranz","doi":"","DOIUrl":"","url":null,"abstract":"The carcinogenicity prediction and battery selection (CPBS) method can be used to predict the probable carcinogenicity of a chemical based on the results of a battery of short-term assays. The method uses Bayesian statistics and the estimated performance characteristics of the assays (i.e., sensitivity and specificity). For routine use, the prior probability of carcinogenicity (or of noncarcinogenicity) is assumed to be unknown and is assigned a nondiscriminatory value of 0.5, i.e., the chemical is assumed to have an equal probability of being a carcinogen or a noncarcinogen, which implies that the expert's intuition regarding the chemical's potential as a carcinogen, based on structural features, known metabolic transformation, or potential electrophilicity, is not taken into consideration. In the present study, it is shown with cyclamate and its metabolite cyclohexlamine that when a battery of assays is used, assigning values to the prior probability between 0.1 and 0.9 has no significant effect on the predicted carcinogenicity. In the view of the fact that the performance of short-term tests is calibrated against known carcinogens and noncarcinogens, and since in the available data bases there is a preponderance of carcinogens, it may be argued that the estimation of sensitivities may be biased toward elevated values. It is shown, however, that when a battery of assays is used, assigning decreased values to the sensitivity does not result in significant effects on the predicted activity of the two test chemicals. Frequently, in the compilation of short-term results within a single assay, different laboratories may report varying results. Heretofore the \"consensus result\" was derived by majority rule. Because the variability in results may have biological significance, and in view of the fact that for a widely used sweetner one might be even more risk-adverse, a modification of Bayes's formula was derived to take these differences into consideration when calculating the probable carcinogenicity of cyclamate and its major metabolite.","PeriodicalId":77750,"journal":{"name":"Molecular toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13598710","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: 0

Carcinogenicity and mutagenicity of N-nitroso compounds. n -亚硝基化合物的致癌性和致突变性。

Molecular toxicology Pub Date : 1987-01-01

W Lijinsky

{"title":"Carcinogenicity and mutagenicity of N-nitroso compounds.","authors":"W Lijinsky","doi":"","DOIUrl":"","url":null,"abstract":"The carcinogenic activities in rats and hamsters and the mutagenic activity in Salmonella of a number of N-nitroso compounds belonging to various classes have been compared. While most directly acting N-nitroso compounds and those requiring metabolic activation are mutagenic with appropriate activation and seem to alkylate DNA in vivo, there are exceptions. Some of these are mutagens that are not carcinogenic; others are carcinogens that are nonmutagenic. Even among the mutagenic carcinogens, there is no quantitative relationship between mutagenic and carcinogenic activities. This implies to directly acting compounds and to those requiring metabolic activation. The lack of congruence between the two activities among the nitrosamines is due to the complexity of the metabolic activating processes leading to formation of proximate carcinogens. The deficiencies in the mutagenesis assay appear to arise from a lack of the necessary enzymes in the liver microsomal fractions used for activation. Nitrosamines bearing oxygen on the beta carbon of an alkyl chain are not oxidized by rat microsomal enzymes and hence are not converted to bacterial mutagens by rat liver microsomes. Bacterial mutagenicity is not a guide to carcinogenic activity of N-nitroso compounds or to the mechanisms by which these compounds induce cancer.","PeriodicalId":77750,"journal":{"name":"Molecular toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14457473","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: 0