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The influence of very low doses of Cisplatin on tumor cell proliferation in vitro and on some hematological and enzymatic parameters of healthy rats. 极低剂量顺铂对体外肿瘤细胞增殖及健康大鼠血液学和酶学指标的影响。
Pub Date : 2003-01-01 DOI: 10.1080/15401420390844500
Elzbieta Malarczyk, Martyna Kandefer-Szerszeń, Anna Jarosz-Wilkołazka

Healthy rats had been treated for 2 or 6 weeks with 1.0 mL of 10(-8) and 10(-16) mg/mL of cisplatin. After 2 weeks of treatment, a significant increase in leukocyte and erythrocyte count and also in hematocrit was observed. Among leukocytes the number of neutrophils and eosinophils significantly increased. Biochemical analyses indicated a decrease in the glycogen content in the liver and kidneys after 2 weeks of treatment with low doses of cisplatin but at the end of the experiment (8th week of experiment) the stores of glycogen increased significantly. Biochemical analyses concerning the activity of some enzymes in the liver revealed a significant increase of peroxidase and acid phosphatase as well as catalase activities after 2 weeks of treatment. However, catalase was induced by a very low concentration of cisplatin, 10(-16) mg/mL. After the cessation of cisplatin treatment the activity of enzymes returned to normal values.Human lung carcinoma cell line A(549) (ECACC No 86012804) was also studied after treatment with the same doses of cisplatin and inhibition of its growth was observed. The results of these experiments strongly indicated that low doses of cisplatin could be stimulating for healthy cells but cytostatic for tumor cells.Possible mechanisms involved in the biological activity of very low cisplatin concentrations are discussed.

健康大鼠分别给予1.0 mL 10(-8)和10(-16)mg/mL顺铂治疗2或6周。治疗2周后,观察到白细胞和红细胞计数以及红细胞压积显著增加。在白细胞中,中性粒细胞和嗜酸性粒细胞的数量显著增加。生化分析显示,低剂量顺铂治疗2周后,肝脏和肾脏的糖原含量下降,但实验结束时(实验第8周)糖原储量明显增加。肝脏中一些酶活性的生化分析显示,治疗2周后,过氧化物酶、酸性磷酸酶和过氧化氢酶活性显著增加。然而,过氧化氢酶被非常低浓度的顺铂(10(-16)mg/mL)诱导。停止顺铂治疗后,酶活性恢复到正常值。用相同剂量的顺铂治疗人肺癌细胞株A(549) (ECACC No 86012804)后也进行了研究,观察到其生长受到抑制。这些实验结果强烈表明,低剂量的顺铂可能对健康细胞有刺激作用,但对肿瘤细胞有抑制作用。讨论了极低浓度顺铂生物活性的可能机制。
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引用次数: 1
Mechanistic basis for nonlinear dose-response relationships for low-dose radiation-induced stochastic effects. 低剂量辐射随机效应非线性剂量-反应关系的机理基础。
Pub Date : 2003-01-01 DOI: 10.1080/15401420390844492
Bobby R Scott, Dale M Walker, Yohannes Tesfaigzi, Helmut Schöllnberger, Vernon Walker

The linear nonthreshold (LNT) model plays a central role in low-dose radiation risk assessment for humans. With the LNT model, any radiation exposure is assumed to increase one's risk of cancer. Based on the LNT model, others have predicted tens of thousands of deaths related to environmental exposure to radioactive material from nuclear accidents (e.g., Chernobyl) and fallout from nuclear weapons testing. Here, we introduce a mechanism-based model for low-dose, radiation-induced, stochastic effects (genomic instability, apoptosis, mutations, neoplastic transformation) that leads to a LNT relationship between the risk for neoplastic transformation and dose only in special cases. It is shown that nonlinear dose-response relationships for risk of stochastic effects (problematic nonlethal mutations, neoplastic transformation) should be expected based on known biological mechanisms. Further, for low-dose, low-dose rate, low-LET radiation, large thresholds may exist for cancer induction. We summarize previously published data demonstrating large thresholds for cancer induction. We also provide evidence for low-dose-radiation-induced, protection (assumed via apoptosis) from neoplastic transformation. We speculate based on work of others (Chung 2002) that such protection may also be induced to operate on existing cancer cells and may be amplified by apoptosis-inducing agents such as dietary isothiocyanates.

线性非阈值(LNT)模型在人类低剂量辐射风险评估中起着核心作用。在LNT模型中,任何辐射暴露都被认为会增加患癌症的风险。根据LNT模型,其他人预测了数万人的死亡与核事故(例如切尔诺贝利)和核武器试验的沉降物造成的放射性物质的环境暴露有关。在这里,我们介绍了一个基于机制的低剂量、辐射诱导的随机效应(基因组不稳定、细胞凋亡、突变、肿瘤转化)模型,该模型仅在特殊情况下导致肿瘤转化风险与剂量之间的LNT关系。研究表明,基于已知的生物学机制,随机效应(有问题的非致死突变,肿瘤转化)风险的非线性剂量-反应关系应该是预期的。此外,对于低剂量、低剂量率、低let辐射,可能存在较大的致癌阈值。我们总结了先前发表的表明癌症诱导的大阈值的数据。我们还提供了低剂量辐射诱导的保护(假设通过细胞凋亡)的证据。根据其他人(Chung 2002)的工作,我们推测这种保护也可能被诱导作用于现有的癌细胞,并可能被诱导凋亡的药物(如膳食异硫氰酸酯)放大。
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引用次数: 50
Mathematical Modeling of Allelopathy. III. A Model for Curve-Fitting Allelochemical Dose Responses. 化感作用的数学建模。3曲线拟合化感化学剂量反应模型。
Pub Date : 2003-01-01 DOI: 10.1080/15401420390844456
De Li Liu, Min An, Ian R Johnson, John V Lovett

Bioassay techniques are often used to study the effects of allelochemicals on plant processes, and it is generally observed that the processes are stimulated at low allelochemical concentrations and inhibited as the concentrations increase. A simple empirical model is presented to analyze this type of response. The stimulation-inhibition properties of allelochemical-dose responses can be described by the parameters in the model. The indices, p% reductions, are calculated to assess the allelochemical effects. The model is compared with experimental data for the response of lettuce seedling growth to Centaurepensin, the olfactory response of weevil larvae to alpha-terpineol, and the responses of annual ryegrass (Lolium multiflorum Lam.), creeping red fescue (Festuca rubra L., cv. Ensylva), Kentucky bluegrass (Poa pratensis L., cv. Kenblue), perennial ryegrass (L. perenne L., cv. Manhattan), and Rebel tall fescue (F. arundinacea Schreb) seedling growth to leachates of Rebel and Kentucky 31 tall fescue. The results show that the model gives a good description to observations and can be used to fit a wide range of dose responses. Assessments of the effects of leachates of Rebel and Kentucky 31 tall fescue clearly differentiate the properties of the allelopathic sources and the relative sensitivities of indicators such as the length of root and leaf.

生物测定技术常用于研究化感物质对植物过程的影响,通常观察到,在低化感物质浓度下,植物过程受到刺激,随着浓度的增加而受到抑制。提出了一个简单的经验模型来分析这类响应。化感剂量反应的刺激抑制特性可以用模型中的参数来描述。计算化感效应的指标p%消减率。利用该模型与实验数据比较了莴苣幼苗生长对半Centaurepensin的反应、象鼻虫幼虫对-松油醇的嗅觉反应、一年生黑麦草(Lolium multiflorum Lam.)、匍匐红羊茅(Festuca rubra L., cv.)的反应。肯塔基蓝草(Poa pratensis L., cv.);Kenblue),多年生黑麦草(L. perenne L., cv.;叛逆高羊茅和肯塔基31高羊茅浸出液对幼苗生长的影响。结果表明,该模型能很好地描述观测值,可用于拟合大范围的剂量响应。通过对Rebel和Kentucky 31高羊茅渗滤液的评价,可以明显区分化感源的特性和根、叶长度等指标的相对敏感性。
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引用次数: 73
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Nonlinearity in biology, toxicology, medicine
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