Lo L W, Stich H F
Mutat Res. 1978 Mar;57(1):57-67. doi: 10.1016/0027-5107(78)90234-8.
The effect of reducing agents on the nitrosation of methylguanidine (MG) and on the in vitro activation of dimethylnitrosamine (DMN) was examined by measuring DNA-repair synthesis (unscheduled incorporation of [3h]TdR), shifts in alkaline sucrose gradients, frequency of chromosome aberrations, and clone-forming capacity of cultured human fibroblasts. The reducing agents examined were sodium ascorbate, cysteine, cysteamine, and propyl gallate. Since the short-term bioassays used can be quantitated, it has become relatively easy to detect the inhibitory action of reducing compounds on the nitrosation reaction of MG and metabolic activation (with S-9 preparation) of the precarcinogen DMN, to measure their effective dose range, and to establish the most effective ratios between inhibitory agent and reactant. The results indicate that DNA-repair synthesis is a suitable short-term test for studying the numerous combinations and premutations between several carcinogenic or non-carcinogenic agents, and for estimating the capacity of inhibitory agents to affect formation and activation of chemical carcinogens.
通过测量DNA修复合成（[3H]TdR的非预定掺入）、碱性蔗糖梯度变化、染色体畸变频率以及培养的人成纤维细胞的克隆形成能力，研究了还原剂对甲基胍（MG）亚硝化作用以及对二甲基亚硝胺（DMN）体外活化的影响。所研究的还原剂有抗坏血酸钠、半胱氨酸、半胱胺和没食子酸丙酯。由于所使用的短期生物测定法可以进行定量，因此检测还原化合物对MG亚硝化反应以及前致癌物DMN代谢活化（用S-9制剂）的抑制作用、测量其有效剂量范围以及确定抑制剂与反应物之间的最有效比例相对容易。结果表明，DNA修复合成是一种合适的短期试验，可用于研究几种致癌或非致癌剂之间的多种组合和预突变，以及估计抑制剂影响化学致癌物形成和活化的能力。
