烟酰胺诱导的小鼠肿瘤组织和非肿瘤组织中的DNA损伤与修复
DNA damage and repair in tumour and non-tumour tissues of mice induced by nicotinamide.
作者信息
Olsson A R, Sheng Y, Pero R W, Chaplin D J, Horsman M R
机构信息
Department of Molecular Ecogenetics, University of Lund, Sweden.
出版信息
Br J Cancer. 1996 Aug;74(3):368-73. doi: 10.1038/bjc.1996.367.
In vivo DNA damage and repair was induced by nicotinamide (NAM) in adenotype 12 virus-induced mouse sarcoma A12B3 and sarcoma F inoculated into CBA mice. DNA damage, NAM and NAD concentrations were measured after in vivo exposure to NAM, in tumours and spleens by alkaline elution and by HPLC analysis. Our results indicate that NAM between 100-1000 mg kg-1 causes a high level of in vivo DNA strand breaks in tumours and normal tissues in mice bearing the immunogenic sarcoma A12B3 but not in the non-immunogenic sarcoma F. The repair process was also delayed by the NAM treatment probably owing to inhibition of the DNA repair enzyme, poly(ADP-ribose)polymerase, as evidenced by accumulation of NAM and NAD. These data are consistent with NAM having a mechanism of action as a radiosensitiser at least in part by DNA repair inhibition. In addition, it should also be considered that high doses of NAM might cause considerable complications to normal tissue in tumour-bearing individuals.
在接种了腺病毒12型诱导的小鼠肉瘤A12B3和肉瘤F的CBA小鼠体内，烟酰胺（NAM）可诱导DNA损伤和修复。通过碱性洗脱和高效液相色谱分析，在体内暴露于NAM后，对肿瘤和脾脏中的DNA损伤、NAM和NAD浓度进行了测量。我们的结果表明，100 - 1000 mg kg-1的NAM会在携带免疫原性肉瘤A12B3的小鼠的肿瘤和正常组织中引起高水平的体内DNA链断裂，但在非免疫原性肉瘤F中则不会。NAM处理也会延迟修复过程，这可能是由于DNA修复酶聚（ADP-核糖）聚合酶受到抑制，NAM和NAD的积累证明了这一点。这些数据与NAM至少部分通过抑制DNA修复而具有放射增敏剂的作用机制一致。此外，还应考虑到高剂量的NAM可能会给荷瘤个体的正常组织带来相当大的并发症。
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