Lowe J K, Brox L, Henderson J F
Cancer Res. 1977 Mar;37(3):736-43.
Mycophenolic acid and virazole are inhibitors of inosinate dehydrogenase and produce growth inhibition and loss of viability in cultured murine lymphoma L5178Y cells. Treatment with 1 muM mycophenolic acid produced the following changes in concentrations of acid-soluble nucleotides: (a) guanosine triphosphate decreased to less than 10% of control within 2 hr; (b) uridine triphosphate and cytidine triphosphate concentrations increased markedly; (c) adenosine triphosphate did not change; (d) deoxyguanosine triphosphate decreased; and (e) thymidine triphosphate increased. DNA synthesis was inhibited by 90% within 2 hr, whereas the incorporation of adenosine into RNA and of leucine into protein were much less affected. Virazole (100 muM) produces similar effects. These biochemical effects of mycophenolic acid, as well as its effects on cell growth, can be prevented by addition of guanylate to the medium. Mycophenolic acid treatment also appears to cause breakdown of high-molecular-weight DNA.
霉酚酸和病毒唑是肌苷酸脱氢酶的抑制剂，可抑制培养的小鼠淋巴瘤L5178Y细胞的生长并使其活力丧失。用1μM霉酚酸处理后，酸溶性核苷酸浓度发生了以下变化：（a）三磷酸鸟苷在2小时内降至对照的10%以下；（b）三磷酸尿苷和三磷酸胞苷浓度显著增加；（c）三磷酸腺苷未发生变化；（d）三磷酸脱氧鸟苷减少；（e）三磷酸胸腺嘧啶核苷增加。2小时内DNA合成被抑制了90%，而腺苷掺入RNA以及亮氨酸掺入蛋白质的过程受影响较小。病毒唑（100μM）产生类似的效果。向培养基中添加鸟苷酸可防止霉酚酸的这些生化作用及其对细胞生长的影响。霉酚酸处理似乎还会导致高分子量DNA的降解。
