Mao J H, Wheldon T E
Department of Radiation Oncology, University of Glasgow, CRC Beatson Laboratories, United Kingdom.
Math Biosci. 1995 Oct;129(2):95-110. doi: 10.1016/0025-5564(94)00053-3.
A stochastic process model for one-, two-, and three-stage malignant transformation has been developed for embryonic and adult mice. The model has been used to study the influence of mutation rate, number of stages required for transformation, and number of stem cells at risk on the kinetics of spontaneous appearance of malignant tumors. As expected, tumors appeared earlier with fewer required mutational stages, higher mutation rate, and greater number of stem cells at risk. However, a notable observation was that tumor latency was more strongly influenced by number of stages and by stem cell number at lower mutation rates than at higher rates. This implies that tumor latency may be a less useful observation when the spontaneous mutation rate is high. In the future, the model will be applied to analysis of tumorigenesis experiments in transgenic mice with p53 genetic abnormalities, subjected to irradiation or chemical tumorigenesis at different stages of development.
已经为胚胎期和成年期小鼠建立了一个用于一阶段、两阶段和三阶段恶性转化的随机过程模型。该模型已被用于研究突变率、转化所需阶段数以及处于风险中的干细胞数量对恶性肿瘤自发出现动力学的影响。正如预期的那样，所需突变阶段数越少、突变率越高以及处于风险中的干细胞数量越多，肿瘤出现得越早。然而，一个值得注意的观察结果是，与高突变率相比，在低突变率下，肿瘤潜伏期受阶段数和干细胞数量的影响更大。这意味着当自发突变率较高时，肿瘤潜伏期可能不是一个很有用的观察指标。未来，该模型将应用于分析具有p53基因异常的转基因小鼠在发育的不同阶段受到辐射或化学致癌作用后的肿瘤发生实验。
