各种身体组织中痕量金属/元素的组成平衡和分布是组织和细胞稳态的关键参与者。低锌水平以及金属硫素素的过度表达与包括前列腺癌在内的各种癌症的发展和进展有关。尽管如此,关于金属稳态的癌症和正常表型的更广泛的元素谱在文献中没有得到很好的阐明.此外,实验动物目前被用作研究癌症的公认模型,但它们在实际癌症组织中的代表性水平尚不清楚.这项研究试图评估目前使用的动物模型的相关性,作为癌症的替代品,并建立它们与人类实际正常和癌症组织的关系。这项研究的主要重点是研究人类尸体的癌症和正常组织中金属浓度和分布的差异关系,以及它们与已建立的代表器官癌症的动物模型的比较。工作假设是,死后看到的元素/金属浓度和分布将显示正常和癌症衍生组织之间以及人类各种组织类型之间的显着差异。老鼠,还有狗.这项研究还建立了关键的元素/金属概况,这些概况可能与三种主要癌症的发展相关。正常人和尸体肺的肿瘤组织,乳房,本研究中使用的肝脏来自美国Biomax公司和相关动物模型(Sprague-dawley和Brown挪威大鼠以及狗;来自杰克逊实验室和密西西比州立兽医实验室,MS),分析要素并检验假设。使用与电感耦合等离子体-原子发射质谱法(ICP-MS)一起使用以确定包括Ag在内的21种元素的浓度和分布所必需的标准化消化程序制备组织样品。Al,As,Ba,Ca,Cd,Co,Cr,Cu,Fe,Mg,Mn,Na,Ni,Pb,Sb,Se,Sr,Tl,V,和Zn。我们的数据支持以下观点:金属/元素稳态对于正常组织功能至关重要,并且元素含量变化,分布,和排名是组织特异性以及癌症和物种特异性。数据分析显示,与该假设一致,动物模型和实际人体组织之间的元素含量和分布概况/排名存在显着差异。结论是,元素稳态对于正常组织功能至关重要,并且其分布和含量的变化对于确定使用动物模型作为研究癌症的替代品至关重要。这些结果是有希望的,并且需要进一步研究以确认动物模型与它们作为用于检查靶向癌症治疗剂的临床前工具的用途的相关性。
The compositional balance and distribution of trace metals/elements in various body tissues are essential key players in tissue and cellular homeostasis. Low Zn levels as well as overexpression of metalothioneins were implicated in the development and progression of various cancers including the prostate. Nonetheless, wider elemental profiles that relate cancer and normal phenotypes with regards to metal homeostasis were not well elucidated in the literature. Moreover, laboratory animals are currently used as accepted models for studying cancer but the level of their representation of actual cancer tissues was not clear. This study is attempting to assess the relevance of animal models currently in use, as surrogates for cancer and establish their relationship to actual normal and cancer tissues from humans. The major focus of this study was to investigate the differential relationship of metal concentrations and profiles in cancer and normal tissues from cadavers of humans and their comparison to established animal models representing organ cancers. The working hypothesis was that elemental/metal concentrations and profiles seen in post mortem will show significant differences between normal and cancer-derived tissues as well as between various tissue types in humans, rats, and dogs. This study also establishes critical elemental/metal profiles that may be relevant in providing correlations with the development of three major cancers. Normal human and tumor tissues of cadaverous lung, breast, and liver used in this study were obtained from US Biomax Company and relevant animal models (Sprague-dawley and Brown Norwegian rats as well as dogs; were obtained from Jackson Laboratories and the Mississippi State Veterinary Laboratory in Pearl, MS), to analyze for elements and test the hypothesis. Tissue samples were prepared using standardized digestion procedures necessary for use with the Inductively Coupled Plasma-Atomic Emission mass Spectrometry (ICP-MS) to determine the concentrations and profiles of 21 elements including Ag, Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn, Na, Ni, Pb, Sb, Se, Sr, Tl, V, and Zn. Our data supports the notion that metal/elemental homeostasis is essential for normal tissue function and that elemental variations in content, distributions, and ranking are tissue specific as well as carcinoma and species-specific. Analysis of data showed significant variations in elemental content and distribution profiles/ranking between animal models and actual human tissues consistent with the hypothesis. It is concluded that elemental homeostasis is essential for normal tissue function and that shifts in their distribution and content are essential in determining the use of animal models as surrogates for studying cancer. These results are promising and warrant further studies to confirm the relevance of animal models in relation to their use as pre-clinical tools for examining targeted cancer therapeutics.