Abstract
Mouse neuroblastoma cells, NB, have been grown in increasing concentrations of mycophenolic acid for greater than 80 passages. A mycophenolic acid resistant neuroblastoma cell line (NB-MyR) has been isolated which is 1000-fold more resistant to mycophenolic acid than NB cells. Fifty percent growth inhibition was caused by 1.6 × 10−7 M and 1.65 × 10−4 M mycophenolic acid for NB and NB-MyR cells respectively. In crude cell lysates the apparant inhibition constant for mycophenolic acid with inosinate dehydrogenase was 6 × 10−8 M and 14 × 10−8 M for NB and NB-MyR cells respectively. Thus the ki for mycophenolic acid was essentially unchanged. The specific activity of inosinate dehydrogenase was 4.9 ± 1.4 and 26.6 ± 2.5 nmole/min/mg protein for NB and NB-MyR cells respectively. The 5.4-fold increase of inosinate dehydrogenase activity in the NB-MyR line may account in part for the increased resistance to mycophenolic acid. Preliminary findings also suggest a 3-fold increase in guanylate synthetase activity for NB-MyR cells as compared to NB cells. Supported by the Alberta Cancer Board grant H-105
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