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1.
F. William Sunderman 《Biological trace element research》1979,1(1):63-86
Experimental observations that pertain to mechanisms of metal carcinogenesis are summarized, with emphasis upon (a) interactions of metals with nucleic acids in vitro; (b) impairment by metals of the fidelity of DNA replication by DNA polymerase in vitro; (c) mutagenicity of metals in microorganisms; (d) cytogenetic aberrations induced by metals in tissue culture cells; (e) induction by metals of neoplastic transformation of tissue culture cells; and (f) nuclear uptake of metals in vivo and concomitant inhibitory effects of metals on synthesis of nucleic acids. Considered
in toto, the experimental data support the somatic mutation hypothesis of chemical carcinogenesis. Sufficient experimental
evidence is available regarding four carcinogenic metals (As, Be, Cr, and Ni) to permit speculations about the molecular reactions
whereby these metals may induce somatic mutations.
This article is an updated outgrowth of a review presented at the A. O. Beckman Conference on the Biochemistry of Cancer that
was held in San Antonio, Texas, on September 6–8, 1978. The earlier draft of this article is being published in the proceedings
volume. 相似文献
2.
Recent reports have provided evidence that selenium is an essential growth factor for cells grown in tissue culture. The aim
of the work reported in this paper was to evaluate mouse fibroblasts as a model for the study of selenium metabolism in mammalian
cells.
The results showed that transformed mouse lung fibroblasts grown in media containing 9.1% bovine serum did not show a growth
response to added selenium as selenite over the range of 10–1000 ng/mL. Uptake of selenium by cells was a direct function
of the selenium concentration in the medium. The rate of uptake varied with the time of exposure of the cells to the selenium,
and to the form of selenium in the medium.
Experiments using radioactive selenium showed that75Se from selenite was rapidly absorbed into the cell wall, but slowly incorporated into the soluble protein fraction.75Se from selenomethionine was more slowly absorbed into the cells, but once inside, it became rapidly incorporated into soluble
cytoplasmic proteins.
Cell fractionation and gel filtration procedures established that75Se from selenite was rapidly incorporated into glutathione peroxidase (GSHpx), whereas75Se from selenomethionine was initially incorporated into a wide spectrum of proteins and only after a longer period did the75Se peak become associated with GSHpx.
These findings suggest fundamental differences exist in the manner in which mammalian cells initially absorb and metabolize
different selenium compounds. 相似文献
3.
Chemical carcinogenesis can be characterized by a sequence of events leading to the development of tumors. Selenium (Se) inhibition
of colon, liver, and lung carcinogens is demonstrated. Using the male Sprague Dawley rat model Se inhibited the colon tumor
incidence in 1,2-dimethylhydrazine (DMH) treated rats and reduced the total number of colon tumors in methylazoxymethanol
(MAM) treated rats. Selenium inhibited 2-acetylaminofluorene (AAF) and 3′-methyl-4-dimethylaminoazobenzene (3′-MeDAB) hepatocarcinogenesis.
The hepatic tumor incidence induced by 3′-MeDAB was reduced by both inorganic Se (Na2SeO3) and by organic Se (Se-yeast) supplements.
In vitro systems have been studied in an effort to decipher the inhibitory properties of Se on the multistage origin of tumors
induced by chemical carcinogens. Current studies suggest that the protective effect of Se against AAF hepatocarcinogenesis
may be correlated with a change in AAF metabolism. The mutagenicity of AAF and AAF metabolites inSalmonella typhimurium TA1538 is decreased by Se. Additionally, Se reduced N-t-OH−AAF induction of sister chromatid exchange (SCE) frequencies in
whole blood cultures, and also reduced aryl hydrocarbon hydroxylase activity using benzo(a) pyrene as substrate.
The comparative effects of antioxidants on DMH induction of colon tumors are presented in detail. Supplements of 4 ppm Se
to the drinking water, 1.2% ascorbic acid (V
c
) to the diet or 0.5% butylated hydroxytoluene (BHT) to the diet of DMH-treated rats reduced the colon tumor incidence of
DMH controls from 64 to 31% (Se), 38% (V
c
), and 43% (BHT). The colon tumor incidence in DMH-treated rats receiving a combination of Se+V
c
increased to 83%, while the combination of Se+BHT decreased the colon tumor incidence to 55%. The growth and survival of
rats provided long-term supplements of 4 ppm Se in the drinking water are compared with untreated controls. 相似文献
4.
I. L. Vovchuk S. A. Petrov 《Biochemistry (Moscow) Supplemental Series B: Biomedical Chemistry》2008,2(3):267-274
The literature and own experimental data on the role of metallocarboxypeptidases in carcinogenesis have been reviewed. The development of various tumors is accompanied by the increase in activity of all groups of these. It is suggested that in some cases carboxypeptidases play a protective role attributed to inhibition of tumor development. 相似文献
5.
Chromate metabolism in liver microsomes 总被引:3,自引:0,他引:3
Karen W. Jennette 《Biological trace element research》1979,1(1):55-62
The carcinogenicity and mutagenicity of various chromium compounds have been found to be markedly dependent on the oxidation
state of the metal. The carcinogen chromate was reduced to chromium(III) by rat liver microsomes in vitro. Metabolism of chromate
by microsomal enzymes occurred only in the presence of either NADPH or NADH as cofactor. The chromium(III) generated upon
metabolism formed a complex with the NADP+ cofactor. Significant binding of chromium to DNA occurred only when chromate was incubated in the presence of microsomes
and NADPH. Specific inhibitors of the mixed function oxidase enzymes, 2′-AMP, metyrapone, and carbon monoxide, inhibited the
rate of reduction of chromate by microsomes and NADPH. The possible relationship of metabolism of chromate and its interaction
with nucleic acids to its carcinogenicity and mutagenicity is discussed. 相似文献
6.
本研究收集了19株不同来源的斑玉蕈品种,通过ITS测序构建其系统发育树,随后根据菌株在木屑培养基与葡萄糖培养基的生长速度对菌株进行分类,选取生长速度差异明显的快、中和慢8株斑玉蕈菌株进行出菇实验及胞内外碳代谢指标的测定,探讨斑玉蕈生产性能与胞内外碳代谢的相关性。研究发现收集到的19株菌株均为斑玉蕈,亲缘关系近,遗传分化程度低;选取出的8株斑玉蕈菌株鲜菇产量与菌丝生长速度呈极显著正相关,菌丝生长越快,出菇产量越高。同时,斑玉蕈菌株鲜菇产量与菌丝湿重、还原糖、可溶性蛋白、滤纸酶(FPase)、CMC-Na酶(CMCase)、木聚糖酶和淀粉酶7个胞外碳代谢指标(ECMI)及胞内葡萄糖、己糖激酶(HK)、丙酮酸激酶(Pyk)、柠檬酸合酶(CS)、α-酮戊二酸脱氢酶(KGDH)和葡萄糖-6-磷酸脱氢酶(G6PD) 6个胞内碳代谢指标(ICMI)呈显著正相关。说明菌丝生长速度快的斑玉蕈品种,胞外基质分解速度更快,提高可吸收碳源的供应,胞内加强对碳的吸收与同化,为菌丝的增殖提供更多原料与能量。本研究分析了斑玉蕈生产性能与胞内外碳代谢的相关性,为斑玉蕈优良品种的鉴别与选育奠定基础。 相似文献
7.
S. C. O'Neill M. Valdeolmillos G. L. Smith D. A. Eisner 《Molecular and cellular biochemistry》1989,89(2):199-203
We have investigated the effects of inhibiting aerobic and/or anaerobic metabolism on contraction, intracellular calcium and pH in single rat ventricular myocytes. Inhibition of aerobic metabolism alone (with CN) had little effect on these variables. However, if anaerobic glycolysis was also inhibited, then the application of CN decreased systolic [Ca3+]i and increased diastolic [Ca2+]i. There was also a development of a diastolic contracture which lagged behind the increase of diastolic [Ca2+]i. These events were accompanied by an intracellular acidosis. The acidosis was shown to depress contraction and perhaps to account for the fact that diastolic [Ca2+]i increased before the contracture. 相似文献
8.
Monitoring hybridoma metabolism in continuous suspension culture at the intracellular level 总被引:2,自引:0,他引:2
A model mouse hybridoma cell line was grown in continuous culture experiments in a serum-free low-protein lipid-free medium.
The steady-state responses of cell numbers, extra- and intracellular metabolite concentrations, substrate and (by) product
consumption/production rates, and yield coefficients were investigated as a function of step changes in the glutamine concentration
of the feed medium. In addition to the commonly performed analysis of metabolites in culture supernatants, we prepared perchloric
acid extracts of cells and determined the amount and the composition of intracellular amino acids and organic acids. Significant
differences were found with respect to intracellular metabolite pools for cells growing at nearly identical specific growth
rates. To our knowledge this is the first time that data on the intracellular concentrations (pools) of amino acids and Krebs
cycle intermediates are reported in the literature that were obtained under carefully defined culture conditions such as those
attained in continuous culture experiments. 相似文献
9.
John R. Arthur Fergus Nicol Geoffrey J. Beckett 《Biological trace element research》1992,33(1-3):37-42
Selenium deficiency impairs thyroid hormone metabolism by inhibiting the synthesis and activity of the iodothyronine deiodinases,
which convert thyroxine (T4) to the more metabolically active 3,3′-5 triiodothyronine (T3). Hepatic type I iodothyronine deiodinase, identified in partially purified cell fractions using affinity labeling with [125I]N-bromoacetyl reverse triiodothyronine, is also labeled with75Se by in vivo treatment of rats with75Se-Na2SeO3. Thus, the type I iodothyronine 5′-deiodinase is a selenoenzyme. In rats, concurrent selenium and iodine deficiency produces
greater increases in thyroid weight and plasma thyrotrophin than iodine deficiency alone. These results indicate that a concurrent
selenium deficiency could be a major determinant of the severity of iodine deficiency. 相似文献
10.
Ivor E. Dreosti Reginald A. Buckley Ian R. Record 《Biological trace element research》1980,2(1):31-39
Studies performed on adult female rats over a period of 10 weeks indicated that the consumption of alcohol (20% v/v) did not
appear to disturb the zinc or copper balance, nor did it adversely affect tissue zinc or copper levels, even in zinc-restricted
animals. On the contrary, higher plasma zinc levels were consistently observed in animals receiving alcohol together with
the experimental diets. 相似文献
11.
The role of selenium in thyroid hormone metabolism and effects of selenium deficiency on thyroid hormone and iodine metabolism 总被引:1,自引:0,他引:1
John R. Arthur Fergus Nicol Geoffrey J. Beckett 《Biological trace element research》1992,34(3):321-325
Selenium deficiency impairs thyroid hormone metabolism by inhibiting the synthesis and activity of the iodothyronine deiodinases,
which convert thyroxine (T4) to the more metabolically active 3,3′–5 triiodothyronine (T3). Hepatic type I iodothyronine deiodinase, identified in partially purified cell fractions using affinity labeling with [125I]N-bromoacetyl reverse triiodothyronine, is also labeled with75Se by in vivo treatment of rats with75Se−Na2SeO3. Thus, the type I iodothyronine 5′-deiodinase is a selenoenzyme. In rats, concurrent selenium and iodine deficiency produces
greater increases in thyroid weight and plasma thyrotrophin than iodine deficiency alone. These results indicate that a concurrent
selenium deficiency could be a major determinant of the severity of iodine deficiency. 相似文献
12.
Yoshinobu Ohira Jack Hegenauer Paul Saltman V. Reggie Edgerton 《Biological trace element research》1982,4(1):45-56
Iron-deficiency anemia leads directly to both reduced hemoglobin levels and work performance in humans and experimental animals.
In an attempt to observe a direct link between work performance and insufficient iron at the cellular level, we produced severe
iron deficiency in female weanling Sprague-Dawley rats following five weeks on a low-iron diet. Deficient rats were compared
with normal animals to observe major changes in hematological parameters, body weight, and growth of certain organs and tissues.
The overall growth of iron-deficient animals was approximately 50% of normal. The ratio of organ weight: body weight increased
in heart, liver, spleen, kidney, brain, and soleus muscle in response to iron deficiency. Further, mitochondria from heart
and red muscle retained their iron more effectively under the stress of iron deficiency than mitochondria from liver and spleen.
Metabolism of iron in normal and depleted tissue was measured using tracer amounts of59Fe administered orally. As expected, there was greater uptake of tracer iron by iron-deficient animals. The major organ of
iron accumulation was the spleen, but significant amounts of isotope were also localized in heart and brain. In all muscle
tissue examined the59Fe preferentially entered the mitochondria. Enhanced mitochondrial uptake of iron prior to any detectable change in the hemoglobin
level in experimental animals may be indicative of nonhemoglobin related biochemical changes and/or decrements in work capacity. 相似文献
13.
《Archives of animal nutrition》2013,67(2):179-189
Balance experiments have demonstrated that growing pigs fed a ration consisting of wheat, barley, extracted soya meal, dicalciumphosphate, and iodine‐free feeding salt utilised 48.8% of the received iodine. The tested supplementary iodine sources included potassium iodide (KI), ethylenediamine dihydroiodide (EDDI), iodine humate (HUI) prepared from iodine acid (HIO3), and the product P containing 0.004% iodine in an oil base (P). The amount of the supplemented iodine was in all cases 1 mg per 1 kg feed. The utilisation of iodine from the supplements reached 93.6, 92.6, 90.7, and 67.9% for KI, EDDI, P, and HUI, respectively. The values were significantly higher compared with controls (P < 0.01). Compared with KI and EDDI, the utilisation of iodine from HUI was significantly lower (P < 0.01). The lower availability of iodine from HUI was probably due to the high binding capacity of humate. The amount of urinary iodine excreted by control pigs receiving in the non‐supplemented ration 147.5 μg iodine per day, was 40.3 μg per day (27.3%). In the pigs receiving in the supplemented ration 1647.5 μg iodine per day, the amount of urinary iodine reached 734.9 to 805.0 μg per day (44.6 to 48.9%). The corresponding values of faecal excretion were 75.6 μg iodine per day (51.2%) for the control pigs and 106.2 to 121.1 μg iodine per day (6.45 to 7.35%) for the pigs fed the supplemented rations. A high amount of 528.6 μg iodine per day (32.1%) was excreted in the faeces by pigs of the group HUI. 相似文献
14.
Philippe Fragu Colette Brianon Sylvain Halpern Eliane Larras-Regard 《Biology of the cell / under the auspices of the European Cell Biology Organization》1988,62(2):145-155
The analytical ion microscope (AIM) makes possible imaging and relative quantitation of multiple stable or labeled elements on an even tissue section, according to their mass. The purpose of this work was to follow at the rat thyroid follicle level the changes in 127I mapping during low iodine diet (LID) in relation to the ability of thyroid to pick up radioiodine (129I) and to synthesize Tg from its precursor, 2H-labeled leucine. The overall picture of images and countings of 127I shows a progressive decrease of the luminal iodine concentration which on day 80 was 10-fold lower than that of control value. In control rat thyroid cell, concentration was 10-fold lower than that of follicular lumina and was unchanged until 35 days, but the size of the cytoplasmic compartment increased, suggesting a redistribution of iodine stores between thyroid cells and follicular lumina. 129I was always found in colloid as well as in cells at all stages. After 35 days of LID, cytoplasmic and luminal radioiodine concentrations decreased. In control rats, [2H]leucine was found mainly in the cells. During LID its localization was evidenced progressively in most of the lumina. The most striking fact was the presence up to 35 days of some large residual follicles with high 127I concentration and low 129I and 2H incorporation. These data demonstrate the follicular heterogeneity of thyroid response to progressive chronic TSH stimulation induced by LID. 相似文献
15.
16.
Charles C. Capen Wesley G. Beamer Barbara J. Tennent Kathryn A. Stitzel 《Mutation research》1995,333(1-2):143-151
Experimental ovarian carcinogenesis has been investigated in inbred and hybrid strains of mice and induced by a diversity of mechanisms including X-irradiation, oocytotoxic xenobiotic chemicals, ovarian grafting to ectopic or orthotopic sites, neonatal thymectomy, mutant genes reducing germ cell populations, and aging. The mechanisms are briefly reviewed whereby disruptions in the function of graafian follicles results in a spectrum of ovarian proliferative lesions including tumors. The findings in mutant mice support the concept of a secondary (hormonally-mediated) mechanism of ovarian carcinogenesis in mice associated with sterility. Multiple pathogenetic factors that either destroy or diminish the numbers of graafian follicles in the ovary result in decreased sex hormone secretion (especially estradiol-17β) leading to a compensatory over-production of pituitary gonadotrophins (particularly luteinizing hormone), which places the mouse ovary at an increased risk to develop tumors. The intense proliferation of ovarian surface epithelium and stromal (interstitial) cells with the development of unique tubular adenomas in response to sterility does not appear to have a counterpart in the ovaries of women. 相似文献
17.
Oncolytic viruses infect, replicate in, and kill cancer cells selectively without harming normal cells. The rapidly expanding clinical development of oncolytic virotherapy is an exciting interdisciplinary field that provides insights into virology, oncology, and immunotherapy. Recent years have seen greater focus on rational design of cancer-selective viruses together with strategies to exploit their immunostimulatory capabilities, ultimately to develop powerful oncolytic cancer vaccines. However, despite great interest in the field, many important experiments are still conducted under optimum conditions in vitro, with many nutrients present in excess and with cellular stress kept to a minimum. Whilst this provides a convenient platform for cell culture, it bears little relation to the typical conditions found within a tumour in vivo, where cells are often subject to a range of metabolic and environmental stresses. Viral infection and cancer will both lead to production of metabolites that are also not present in media in vitro. Understanding how oncolytic viruses interact with cells exposed to more representative metabolic conditions in vitro represents an under-explored area of study that could provide valuable insight into the intelligent design of superior oncolytic viruses and help bridge the gap between bench and bedside. This review summarises the major metabolic pathways altered in cancer cells, during viral infection and highlights possible targets for future studies. 相似文献
18.
19.
A survey based on 838, samples of milk obtained from 537 dairies covering 70 of 95 districts in France was organized to assess
iodine content of milk and its contribution to total intake. Iodine levels were significantly higher in winter than in summer.
Very low iodine contents (<25 μg I/kg) were found in the eastern part of the country (the Vosges, Jura, and the Alpes) and
the Massif Central. During milk processing, much of the iodine is lost in the whey. The other significant sources of dietary
iodine are fish and eggs. Iodized salt is sold only to households and not to industry. Even if about 20% of the iodine is
lost over the first 3 mo, salt remains the main source for this trace element. It is concluded that, if iodized salt is not
provided systematically for both domestic and agro-industrial use, then milk may be the most important source of iodine. This
key role may explain seasonal and geographical variations in the frequencies of goiter in France. 相似文献
20.
In the present work dynamic changes of free intracellular amino acid pools during autonomous oscillations of Saccharomyces cerevisiae were quantified in glucose-limited continuous cultivations. At a dilution rate of D = 0.22 h(-1) cyclic changes with a period of 120 min were found for many variables such as carbon dioxide production rate, dissolved oxygen, pH, biomass content, and various metabolite concentrations. On the basis of the observed dynamic patterns, free intracellular amino acids were classified to show oscillatory, stationary, or chaotic behavior. Amino acid pools such as serine, alanine, valine, leucine, or lysine were subjected to clear oscillations with a frequency of 120 min, identical to that of other described cultivation variables, indicating that there is a direct correlation between the periodic changes of amino acid concentrations and the metabolic oscillations on the cellular level. The oscillations of these amino acids were unequally phase-delayed and had different amplitudes of oscillation. Accordingly, they exhibited different patterns in phase plane plots vs. intracellular trehalose. Despite the complex and marked metabolic changes during oscillation, selected intracellular amino acids such as histidine, threonine, isoleucine, or arginine remained about constant. Concentrations of glutamate and glutamine showed a chaotic behavior. However, the ratio of glutamate to glutamine concentration was found to be oscillatory, with a period of 60 min and a corresponding figure eight-shaped pattern in a plot vs. trehalose concentration. Considering the described diversity, it can be concluded that the observed periodic changes are neither just the consequence of low or high rates of protein biosynthesis/degradation nor correlated to changing cell volumes during oscillation. The ratio between doubling time (189 min) and period of oscillation of intracellular amino acids (120 min) was 1:6. The fact that there is a close relationship between doubling time and period of oscillation underlines that the described autonomous oscillations are cell-cycle-associated. 相似文献