Comparison of glutathione (GSH) content of tumor cells grown in vivo and in vitro

The authors studied the changes in GSH when human and rodent tumor cells were grown in vitro and in vivo. Three human (A431, Hep3, ME180) and two murine (KHT, Rif-1) cell lines were used. GSH was assayed by HPLC. The average GSH of human cells grown in vitro was 8.1, 10.9 and 17 fmol/cell for ME180, A431 and Hep3 cells, respectively. These cells were also grown as tumors in nude mice. Following dissociation, a 90% pure population of neoplastic cells was isolated by centrifugal elutriation (CE) and assayed for GSH. In contrast to the in vitro results, cells grown in vivo showed a 2-3 fold reduction in GSH values (range = 3-4.4 fmol/cell). The GSH of murine tumor cells grown in vitro was lower than that of human cells (3.3 and 6.8 fmol/cell for Rif-1 and KHT). Similar to the human cells, the GSH of KHT dropped 3 fold when these cells were grown in vivo and isolated after dissociation and CE. Although the average volume of tumor cells grown in vivo in all models was lower than that of cells grown in vitro, this difference could not account for the differences in GSH values observed when in vitro and in vivo cells were compared. Biopsy samples were obtained from tumors, with values ranging from 1.9-5.3 mmol/kg. However, interpretation of GSH values obtained from biopsies is complicated by the presence of significant numbers of host cells (20-50%) in these specimens