Moolten F L
Cancer Res. 1986 Oct;46(10):5276-81.
The lack of highly exploitable biochemical differences between normal tissues and some tumors can theoretically be circumvented by a strategy utilizing gene insertion prophylactically to create tissue mosaicism for drug sensitivity, thereby ensuring that any tumor arising clonally will differ from part of the normal cell population. Elements of the strategy were tested with neoplastic BALB/c murine cell lines bearing the herpes thymidine kinase gene. Exposure to the herpes thymidine kinase-specific substrate 9-([2-hydroxy-1-(hydroxymethyl)ethoxy]methyl)guanine ablated the clonogenic potential of the cells in vitro, and administration of this drug to BALB/c mice bearing tumors produced by the cell lines uniformly induced complete regression of the tumors. The observed responses to therapy imply that the strategy may prove valuable when the genetic technology needed for its human implementation becomes available.
理论上，正常组织与某些肿瘤之间缺乏易于利用的生化差异这一问题，可以通过一种策略来规避。该策略预防性地利用基因插入来创建对药物敏感的组织镶嵌性，从而确保任何克隆性产生的肿瘤都将与部分正常细胞群体不同。该策略的要素已在携带疱疹胸苷激酶基因的BALB/c小鼠肿瘤细胞系中进行了测试。暴露于疱疹胸苷激酶特异性底物9 -（[2 - 羟基 - 1 -（羟甲基）乙氧基]甲基）鸟嘌呤会消除细胞在体外的克隆形成潜力，将这种药物给予携带由这些细胞系产生的肿瘤的BALB/c小鼠，会一致地诱导肿瘤完全消退。观察到的对治疗的反应表明，当该策略在人类中实施所需的基因技术可用时，它可能会被证明是有价值的。
