INTRACELLULAR GLUTATHIONE IN HUMAN CANCER CELL LINES: CORRELATION TO DRUG SUSCEPTIBILITY

Abstract

Glutathione (GSH) is an important antioxidant involved in a variety of biochemical and biological processes. The 60 human cancer cell lines of the National Cancer Institute drug screening panel were measured for total intracellular GSH. An enzyme recycling assay was chosen based on its specificity and sensitivity (Tietze, F. 1969). All cell lines were assayed in triplicate for protein and GSH content, expressed in nmol/mg protein. Renal GSH levels were uniformly low, and the only tissue to display a homogeneous arrangement. Using a pattern-matching computer program, COMPARE, GSH concentrations were correlated with patterns of drug response from the standard agent database, consisting of 174 agents with putative mechanisms of action assigned. Pearson correlation coefficients were modest, indicating no strong associations. No enrichments in any particular mechanism of drug action were associated with GSH levels indicating that constitutive GSH levels do not appear to be directly responsible for drug resistance. In addition, GSH levels were used to complement recent measurements of GSH associated enzymes (Tew, et al. 1996). GSH did not correlate with any of its associated enzymes. However, there was a negative correlation between GSH and y-glutamyl transpeptidase, indicating that lower levels of GSH are associated with y-glutamyl transpeptidase. It can be speculated that changes in GSH levels as a result of toxic insult may be of more significance in determining drug resistance than constitutive GSH concentrations.