This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Allalunis-Turner, M. J. Articles by Siemann, D. W. Search for Related Content PubMed PubMed Citation Articles by Allalunis-Turner, M. J. Articles by Siemann, D. W.

Comparison of Glutathione Levels in Rodent and Human Tumor Cells Grown in Vitro and in Vivo¹

Division of Experimental Therapeutics and Department of Radiation Oncology, University of Rochester Cancer Center, Rochester, New York 14642

Cellular glutathione (GSH) levels were compared in human and rodent tumor cells grown both in vivo and in vitro. Three human (A431, HEp3, ME180) and two murine (KHT and RIF-1) tumor cell lines were used. The average GSH contents for exponentially growing human cells in vitro were 14.2, 10.9, and 17.0 fmol/cell for ME180, A431, and HEp3 cells, respectively. These cells also were grown as tumors in nude mice. Following dissociation, >90% pure populations of neoplastic and nonneoplastic cells were isolated by centrifugal elutriation prior to GSH determination. The data showed that the GSH levels of the tumor associated host cells were appreciably lower than those of the neoplastic cells. In addition, in contrast to the values obtained for the exponential cells, neoplastic cells grown in vivo showed a 2- to 3-fold reduction in GSH. However, the values for in vivo cells were similar to those obtained for the same tumor cells grown in vitro in the plateau phase. Compared to the human tumor cells the GSH contents of murine tumor cells always were lower. For example, RIF-1 and KHT cells in the exponential growth phase had GSH contents of 3.3 and 7.5 fmol/cell, respectively. Also, as was observed with the human cells, the GSH content of KHT cells in plateau phase of growth was 2–3 times less than that of cells in the exponential phase of growth. Similarly, the GSH content of KHT cells grown as in situ tumors prior to dissociation and isolation by centrifugal elutriation also was reduced by a factor of 3 compared to exponential phase cells. Although the average volume of tumor cells grown in vivo was less than that of cells grown in vitro, this did not account for the differences in GSH values observed when in vitro and in vivo derived cells were compared. Finally, GSH measurements made on multiple biopsies of individual human tumor xenografts varied by a factor of 2–3 within each tumor type studied. This variation, likely due to host cell fluctuations, may present a complicating feature in the interpretation of solid tumor GSH levels.

¹ This research was supported by USPHS grants CA-11051 and CA-36858, awarded by the National Cancer Institute, Department of Health and Human Services. The support of the Cell Separation and Flow Cytometry Facility as well as the Animal Tumor Research/Xenograft Facility of the University of Rochester Cancer Center is gratefully acknowledged.

² Recipient of a fellowship from the Alberta Heritage Foundation for Medical Research. Present address: Department of Radiobiology, Cross Cancer Institute, 11560 University Ave., Edmonton AB, Canada, T6G 1Z2.

³ To whom requests for reprints should be addressed, at University of Rochester Cancer Center, 601 Elmwood Ave., Box 704, Rochester, NY 14642, USA.

Received 9/21/87. Revised 1/29/88. Accepted 4/ 6/88.

This article has been cited by other articles:

				S. Gunnarsdottir, M. Rucki, and A. A. Elfarra Novel Glutathione-Dependent Thiopurine Prodrugs: Evidence for Enhanced Cytotoxicity in Tumor Cells and for Decreased Bone Marrow Toxicity in Mice J. Pharmacol. Exp. Ther., April 1, 2002; 301(1): 77 - 86. [Abstract] [Full Text] [PDF]