Fujimoto W Y, Subak-Sharpe J H, Seegmiller J E
Proc Natl Acad Sci U S A. 1971 Jul;68(7):1516-9. doi: 10.1073/pnas.68.7.1516.
Cultured fibroblasts established from skin biopsies from patients with the Lesch-Nyhan syndrome are deficient in hypoxanthine-guanine phosphoribosyl-transferase (EC 2.4.2.8) activity. This deficiency makes possible the use of chemicals that select either for or against deficient variants in cultured fibroblasts. Two-way selection has been achieved by the use of 6-thioguanine, which selects for the deficient mutant, and azaserine, which selects to some extent for the normal allele in mixed cultures, as well as in cultures from heterozygotes. Theoretical considerations predict that the phenomenon of metabolic cooperation would tend to reinforce the former and to weaken the latter type of selection, and this is in accordance with the experimental findings.
从患有莱施-奈恩综合征患者的皮肤活检样本中建立的培养成纤维细胞,其次黄嘌呤-鸟嘌呤磷酸核糖转移酶(EC 2.4.2.8)活性存在缺陷。这种缺陷使得利用化学物质来选择培养成纤维细胞中缺陷型或正常型变体成为可能。通过使用6-硫鸟嘌呤实现了双向选择,6-硫鸟嘌呤可选择缺陷型突变体,而重氮丝氨酸在混合培养物以及杂合子培养物中能在一定程度上选择正常等位基因。理论上的考量预测,代谢合作现象会倾向于加强前一种选择并削弱后一种选择,这与实验结果相符。