Bala M, Jain V
Department of Biocybernetics, Institute of Nuclear Medicine and Allied Sciences, Lucknow Marg, Delhi, India.
Indian J Biochem Biophys. 1997 Dec;34(6):483-93.
Cellular and genomic effects of post-treatment repair modulation by 2-deoxy-D-glucose (2-DG) and yeast extract were studied in 8-MOP + UVA treated cells of Saccharomyces cerevisiae. The type of lesions and their repair in phosphate buffer glucose (PBG) differed with UVA dose. At low UVA dose (1.4 kJ/m2), lesions were sublethal and mutagenic and did not repair by recombinogensis. The fraction of potentially lethal lesions and lesions repaired by recombinogenesis increased with UVA dose. Cellular repair in PBG was largely error-free and was inhibited by 2-DG. Yeast extract enhanced cellular repair and also recombinogensis; 2-DG in presence of yeast extract promoted error-prone repair. Pulsed-field gel electrophoresed chromosomal DNA bands did not show observable alterations immediately after 8-MOP + UVA treatment. On post-treatment incubation in PBG, the intensity ratio (rho n), of each band altered in a biphasic manner showing decrease first, followed by either increase or no change upto 24 hr depending upon UVA exposure dose. Presence of 2-DG in PBG inhibited decrease in rho n in a concentration dependent manner. Yeast extract reduced the time of first phase of DNA repair. 2-DG and yeast extract together reduced the time of first phase of repair and also inhibited the subsequent increase in rho n, which was observed in the case of yeast extract in PBG. It is proposed that (i) 2-DG in PBG inhibits excision of DNA damage and error-free repair; (ii) yeast extract stimulates the error-prone repair associated with cell cycle and recombinogenesis; (iii) 2-DG in presence of yeast extract allows excision of damage but inhibits build up through recombinogenesis inducing instead, cell cycle associated error-prone repair. A simple schematic model has been proposed to explain these events.
在经8-甲氧基补骨脂素（8-MOP）+紫外线A（UVA）处理的酿酒酵母细胞中，研究了2-脱氧-D-葡萄糖（2-DG）和酵母提取物对处理后修复调节的细胞和基因组效应。在磷酸缓冲葡萄糖（PBG）中，损伤类型及其修复情况随UVA剂量而不同。在低UVA剂量（1.4 kJ/m2）下，损伤是亚致死性和致突变性的，且不能通过重组修复。潜在致死性损伤和通过重组修复的损伤比例随UVA剂量增加。PBG中的细胞修复在很大程度上是无差错的，并被2-DG抑制。酵母提取物增强细胞修复以及重组；在酵母提取物存在下，2-DG促进易错修复。脉冲场凝胶电泳的染色体DNA条带在8-MOP + UVA处理后立即未显示出可观察到的改变。在PBG中处理后孵育时，每条带的强度比（ρn）呈双相变化，首先显示降低，随后根据UVA暴露剂量在24小时内要么增加要么不变。PBG中2-DG的存在以浓度依赖方式抑制ρn的降低。酵母提取物缩短了DNA修复第一阶段的时间。2-DG和酵母提取物共同缩短了修复第一阶段的时间，并且还抑制了随后ρn的增加，这在PBG中酵母提取物的情况下可以观察到。有人提出：（i）PBG中的2-DG抑制DNA损伤的切除和无差错修复；（ii）酵母提取物刺激与细胞周期和重组相关的易错修复；（iii）在酵母提取物存在下，2-DG允许损伤切除，但抑制通过重组的积累，而是诱导与细胞周期相关的易错修复。已提出一个简单的示意图模型来解释这些事件。
