DEOXYRIBONUCLEOSIDE TRIPHOSPHATE POOLS AND GROWTH OF GLUTATHIONE-DEPLETED 3T6 MOUSE FIBROBLASTS

Buthionine sulfoximine (BSO) selectively blocks g-glutamylcysteine syn thetase and thereby depletes cells of glutathione (GSH). In cultures o f exponentially growing 3T6 mouse fibroblasts, 0.1 mM BSO rapidly stop ped GSH synthesis after treatment for 12 hours. The GSH-depleted cells grew as well as control 3T6 cells with no decrease in DNA synthesis. Furthermore, the pools of deoxyribonucleoside triphosphates (dNTPs), t ypically tightly regulated in cultured cells, did not change in size. Ribonucleotide reductase catalyzes the reduction of all four ribonucle otides and occupies a key position in dNTP regulation. Our data sugges t that the GSH-glutaredoxin (a GSH-dependent disulfide-oxidoreductase) system is not the sole/major hydrogen carrier from NADPH for the redu ction of ribonucleoside diphosphates by ribonucleotide reductase. (C) 1996 Academic Press, Inc.