Pitot H C
McArdle Laboratory for Cancer Research, Departments of Oncology and Pathology, University of Wisconsin, Madison 53706, USA.
Mutat Res. 1995 Dec;333(1-2):3-14. doi: 10.1016/0027-5107(95)00125-5.
The principal characteristic of neoplasia is its inherited alteration of genetic expression. The regulation of gene expression may be altered both by mutational events and by environmental mediators. During carcinogenesis the permanent alterations in genetic expression resulting from mutations occur primarily during the final stage of progression when biological malignancy becomes evident. During the preceding reversible stage of promotion, alteration and genetic expression are the result of the chronic stimulation of an altered (initiated) cell responding to the environmental mediator or promoting agent. A major mechanism of this effect occurs by receptors exhibiting specificity for the mediator and for their interaction with the genome. Withdrawal of the promoting agent prior to the genetic alterations characteristic of the stage of progression leads to a reversal of the effects of the promoting agent and the death by apoptosis of most cells in the stage of promotion. Carcinogenesis mediated by the chronic ligand (promoting agent)-receptor interaction increases the probability of the development of the stage of progression; thus alteration or prevention of the stage of promotion by removal of the promoting agent or inhibition of its action remains the best opportunity for cancer prevention. Application of the reversible promoting agent-receptor interaction to specific environmental circumstances where such plays a major role can lead to a more rational risk estimation of promoting agents for the human population.
肿瘤形成的主要特征是其遗传表达的遗传性改变。基因表达的调控可能因突变事件和环境介质而改变。在致癌过程中，由突变导致的遗传表达的永久性改变主要发生在进展的最后阶段，此时生物学恶性变得明显。在先前促进的可逆阶段，改变和遗传表达是对环境介质或促进剂作出反应的改变（启动）细胞受到慢性刺激的结果。这种效应的一个主要机制是受体对介质及其与基因组的相互作用表现出特异性。在进展阶段特征性的遗传改变之前撤回促进剂会导致促进剂的作用逆转，并且促进阶段的大多数细胞通过凋亡死亡。由慢性配体（促进剂）-受体相互作用介导的致癌作用增加了进展阶段发展的可能性；因此，通过去除促进剂或抑制其作用来改变或预防促进阶段仍然是预防癌症的最佳机会。将可逆的促进剂-受体相互作用应用于其起主要作用的特定环境情况，可以对人群的促进剂进行更合理的风险评估。
