Pardini C, Mariani L, Voliani M, Rainaldi G, Citti L
Istituto di Mutagenesi e Differenziamento CNR, Pisa, Italy.
Mutat Res. 1992 Jan;275(1):1-6. doi: 10.1016/0921-8734(92)90002-7.
The ability to repair 'mis-instructive', O6-methylguanine, and 'non-instructive', AP sites, DNA lesions in Fischer 344 rat livers at various ages was determined. Different behaviours were observed. While the AP-endodesoxyribonuclease enzymes displayed a high constant level throughout the animals' lifetime, the O6-methylguanine-DNA methyltransferase activity presented a stepwise modulation (DNA normalisation of results): the O6-MT activity significantly increased within the first month of animal life and enhanced again after 6 months reaching a maximum plateau in the 12-18-month-old animals. Thereafter a net significant decrease of O6-MT enzyme was detected in the 24-month-old group. While the repair of the widely formed AP sites appeared uniformly efficient like 'house keeping' functions, the removal of the rare precancerous O6-methylguanine is age-dependent indicating a decreased protection of the youngest and oldest animals against this 'mis-instructive' damage. However, any extrapolation of the age-associated cancer risk needs further assessment.
测定了不同年龄的Fischer 344大鼠肝脏修复“错误指导”的O6-甲基鸟嘌呤和“非指导”的AP位点（DNA损伤）的能力。观察到了不同的行为。虽然AP-内切脱氧核糖核酸酶在动物的整个生命周期中都呈现出高恒定水平，但O6-甲基鸟嘌呤-DNA甲基转移酶活性呈现出逐步调节（对结果进行DNA标准化）：O6-MT活性在动物生命的第一个月内显著增加，并在6个月后再次增强，在12至18个月大的动物中达到最大平台期。此后，在24个月大的组中检测到O6-MT酶有显著的净减少。虽然广泛形成的AP位点的修复像“管家”功能一样均匀有效，但罕见的癌前O6-甲基鸟嘌呤的去除是年龄依赖性的，这表明最年幼和最年长的动物对这种“错误指导”损伤的保护作用降低。然而，与年龄相关的癌症风险的任何外推都需要进一步评估。
