Context:Although carcinogenesis is a multi-factorial process, the mutability and the capacity of cells to proliferate are among the major features of the cells that contribute together to the initiation and promotion steps of cancer formation. Particularly, mutability can be quantified by hyper-recombination rate assessed with specific plasmid assay, hypoxanthine-guanine phosphoribosyltransferase (HPRT) mutations frequency rate, or MRE11 nuclease activities. Cell proliferation can be assessed by flow cytometry by quantifying G2/M, G1 arrests, or global cellular evasion. Methods: All these assays were applied to skin untransformed fibroblasts derived from eight major cancer syndromes characterized by their excess of relative cancer risk (ERR). Results: Significant correlations with ERR were found between hyper-recombination assessed by the plasmid assay and G2/M arrest and described a third-degree polynomial ERR function and a sigmoidal ERR function, respectively. The product of the hyper-recombination rate and capacity of proliferation described a linear ERR function that permits one to better discriminate each cancer syndrome. Conclusions: Hyper-recombination and cell proliferation were found to obey differential equations that better highlight the intrinsic bases of cancer formation. Further investigations to verify their relevance for cancer proneness induced by exogenous agents are in progress.
背景：尽管癌变是一个多因素过程，但细胞的突变能力和增殖能力是促成癌症形成起始与促进阶段的主要细胞特征。具体而言，突变性可通过特定质粒检测评估的超高重组率、次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HPRT）突变频率或MRE11核酸酶活性进行量化。细胞增殖能力可通过流式细胞术量化G2/M期阻滞、G1期阻滞或整体细胞逃逸来评估。方法：本研究对八种具有高相对癌症风险（ERR）特征的主要癌症综合征患者的皮肤未转化成纤维细胞应用了上述所有检测方法。结果：通过质粒检测评估的超高重组率与G2/M期阻滞均与ERR存在显著相关性，分别符合三次多项式ERR函数和S型ERR函数。超高重组率与增殖能力的乘积呈现线性ERR函数关系，能更好地区分各癌症综合征。结论：超高重组与细胞增殖遵循不同的数学方程，这更清晰地揭示了癌症形成的内在基础。目前正在进一步研究以验证其与外源性因素诱导的癌症易感性之间的关联。
肿瘤(癌症)患者之家