Kma L, Sharan R N
Radiation and Molecular Biology Unit, Department of Biochemistry, North-Eastern Hill University, Umshing, Shillong, 793022, India.
Mol Cell Biochem. 2006 Aug;288(1-2):143-9. doi: 10.1007/s11010-006-9130-x. Epub 2006 Apr 1.
Efforts to identify an easy and convenient biomarker of carcinogenesis with potentials of application in mass screening program continue. In a series of investigations on mice exposed to different carcinogens, poly-ADP-ribosylation (PAR) of cellular proteins of different tissues has been shown to be a potential biomarker of carcinogenesis. Because blood based biomarker of carcinogenesis offers significant advantage in its use in a cancer screening program, this investigation was undertaken to find correlations between initiation of carcinogenesis and PAR of bone marrow cell (BMC) and blood lymphocyte (BL) proteins in mice chronically exposed to low dose of dimethylnitrosamine (DMN) for up to four weeks in vivo. The exposure was either alone or in combination with 3-aminobenzamide (3-AB), an inhibitor of PAR. Total PAR of cellular proteins and of histone H1 protein were monitored by slot and Western blot immunoprobe assays, respectively. The PAR of total cellular proteins as well as of histone H1 was down-regulated in duration of exposure dependent manners. The results suggest that BMC and BL mirrored status of PAR in other tissues. This finding opens up the possibility of using PAR as a biomarker of carcinogenesis in a blood based test utilizing immunoprobe assay of cellular PAR.
人们仍在努力寻找一种易于使用且方便的致癌生物标志物,以期应用于大规模筛查项目。在一系列针对接触不同致癌物的小鼠的研究中,不同组织细胞蛋白的多聚ADP核糖基化(PAR)已被证明是一种潜在的致癌生物标志物。由于基于血液的致癌生物标志物在癌症筛查项目中具有显著优势,因此本研究旨在探究长期在体内接触低剂量二甲基亚硝胺(DMN)长达四周的小鼠中,致癌作用的起始与骨髓细胞(BMC)和血液淋巴细胞(BL)蛋白的PAR之间的相关性。暴露方式为单独使用DMN或与PAR抑制剂3-氨基苯甲酰胺(3-AB)联合使用。分别通过狭缝印迹和蛋白质免疫印迹法检测细胞蛋白和组蛋白H1蛋白的总PAR。细胞总蛋白以及组蛋白H1的PAR均以暴露时间依赖性方式下调。结果表明,BMC和BL反映了其他组织中PAR的状态。这一发现为利用细胞PAR免疫印迹法在基于血液的检测中使用PAR作为致癌生物标志物开辟了可能性。