Cohen S M
University of Nebraska Medical Center, Omaha 68198-3135, USA.
Toxicol Lett. 1995 Dec;82-83:15-21. doi: 10.1016/0378-4274(95)03542-7.
DNA replication does not have 100% fidelity. Consequently, a chemical can increase the risk of cancer either by directly damaging DNA (genotoxic) or by increasing the number of cell replications, or both. Increased cell proliferation can be produced by increasing cell births (by direct mitogenesis or regeneration following toxicity), or decreasing cell deaths (by inhibiting apoptosis or differentiation). Cell proliferation can affect the dose-response curve for genotoxic carcinogens and is the basis for carcinogenicity by nongenotoxic agents. Bladder carcinogens will be used to illustrate these mechanisms, and their implications with respect to human risk assessment will be presented.
DNA复制并非具有100%的保真度。因此，一种化学物质可通过直接损伤DNA（基因毒性）或增加细胞复制数量，或两者兼而有之，来增加患癌风险。细胞增殖增加可通过增加细胞生成（通过直接有丝分裂或毒性后的再生）或减少细胞死亡（通过抑制细胞凋亡或分化）来实现。细胞增殖可影响基因毒性致癌物的剂量反应曲线，并且是非基因毒性剂致癌性的基础。将以膀胱致癌物为例来说明这些机制，并阐述其对人类风险评估的意义。
