Parodi S, Malacarne D, Taningher M
Department of Oncology, University of Genova, Italy.
Toxicol Lett. 1992 Dec;64-65 Spec No:621-30. doi: 10.1016/0378-4274(92)90240-k.
In the classical two-stage models of carcinogenesis, initiation has been usually related to a DNA-damage/gene-mutation event, while promotion has been related to the non-genotoxic effects of clonal expansion of preneoplastic cells and/or modulation of cell differentiation. It is now clear that the process of carcinogenesis is linked to more than one irreversible alteration in the genome. Likewise, we can envisage that non-genotoxic events can take place after perhaps 0, 1, 2 or more irreversible alterations in the genome. Initiating and promoting activities of a chemical can be considered clearly separated in theory, but in practice, the chemicals we work with only rarely will be purely of the genotoxic or non-genotoxic type. We will discuss an empirical approach to classify genotoxic or prevalently non-genotoxic chemical carcinogens. For prevalently non-genotoxic carcinogens we will analyze what fraction of them can be detected as promoters of in vivo rat liver carcinogenesis. We will analyze carcinogenic potency of genotoxic and non-genotoxic carcinogens.
在经典的两阶段致癌模型中，引发通常与DNA损伤/基因突变事件相关，而促进则与癌前细胞克隆扩增的非遗传毒性效应和/或细胞分化调节相关。现在很清楚，致癌过程与基因组中不止一种不可逆改变有关。同样，我们可以设想，非遗传毒性事件可能在基因组发生0、1、2次或更多次不可逆改变之后发生。一种化学物质的引发和促进活性在理论上可以被明确区分，但在实际中，我们所研究的化学物质很少会是纯粹的遗传毒性或非遗传毒性类型。我们将讨论一种对遗传毒性或主要为非遗传毒性的化学致癌物进行分类的经验方法。对于主要为非遗传毒性的致癌物，我们将分析其中有多少比例可以被检测为体内大鼠肝癌发生的促进剂。我们将分析遗传毒性和非遗传毒性致癌物的致癌效力。
