Expression of gamma-glutamylcysteine synthetase (gamma-GCS) and multidrug resistance-associated protein (MRP), but not human canalicular multispecific organic anion transporter (cMOAT), genes correlates with exposure of human lung cancers to platinum drugs.

Taken together, these and our results suggest that increased y-GCS expression may be an index of both increased GSH levels and GS-X pump activity and therefore could be a useful drug resistance marker in a clinical setting. To our knowledge, no detailed description of steady-state y- GCSI mRNA levels in clinical samples has been reported, and therefore we could not compare our results with those of others. However, it is not surprising that y-GCSl expression showed a highly significant correlation with y-GCSh expression and ante- mortem platinum drug exposure history, because in vitro studies have demonstrated functional cooperation of y-GCSh and y-GCSl in GSH synthesis (Huang et al, 1993) and possibly in the GSH- mediated drug resistance mechanism (Mulcahy et al, 1995).

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