Hung C F, Wong K T, Tsai C I, Lin C S, Chung J G
Department of Pediatrics, Jen-Ai Hospital, Tali, Taichung, Taiwan.
Acta Paediatr Taiwan. 2000 May-Jun;41(3):133-5.
Arylamine N-acetylation capacity by the N-acetyltransferase (NAT) may be an important causative factor in the initiation of cancer. Arylamine-DNA adducts formation have been correlated with the carcinogenic effect of heterocyclic aromatic amines. NAT activity in rat glial tumor cells was measured by high performance liquid chromatography (HPLC) using 2-aminofluorene (2-AF) and p-aminobenzoic acid (PABA) as substrares. 2-AF-DNA adducts formation in rat glial tumor cells was investigated by gamma-[32p]-dATP and HPLC using 2-aminofluorene as substrates. The activities (Mean +/- SD) of NAT in rat glial cells was 1.08 +/- 0.18 nmol/min/mg protein for the acetylation of 2-aminofluorene (n = 12), and 0.96 +/- 0.16 nmol/min/mg protein for the acetylation of p-aminobenzoic acid (n = 12). 2-AF-DNA adducts formation in rat glial tumor cells with 30 microM and 60 microM AF were 0.48 +/- 0.16 and 0.70 +/- 0.12 pmol/mg DNA, respectively. The results indicate that NAT was present in rat glial tumor cells, activating AF to become a metabolite able to bind covalently with DNA to form 2-AF-DNA.
由N - 乙酰基转移酶(NAT)介导的芳胺N - 乙酰化能力可能是癌症发生的一个重要致病因素。芳胺 - DNA加合物的形成与杂环芳香胺的致癌作用相关。使用2 - 氨基芴(2 - AF)和对氨基苯甲酸(PABA)作为底物,通过高效液相色谱法(HPLC)测定大鼠胶质瘤细胞中的NAT活性。以2 - 氨基芴为底物,通过γ - [32P] - dATP和HPLC研究大鼠胶质瘤细胞中2 - AF - DNA加合物的形成。大鼠神经胶质细胞中NAT的活性(平均值±标准差),对于2 - 氨基芴的乙酰化反应为1.08±0.18 nmol/分钟/毫克蛋白质(n = 12),对于对氨基苯甲酸的乙酰化反应为0.96±0.16 nmol/分钟/毫克蛋白质(n = 12)。在含有30 microM和60 microM AF的大鼠胶质瘤细胞中,2 - AF - DNA加合物的形成量分别为0.48±0.16和0.70±0.12 pmol/毫克DNA。结果表明,NAT存在于大鼠胶质瘤细胞中,可将AF激活为一种能够与DNA共价结合形成2 - AF - DNA的代谢产物。