Selective Killing of Oncogenic Human Cells Cocultivated With Normal Human Fibroblasts2

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Abstract
Histidinol and theophylline reversibly arrested the growth of low-passage human foreskin fibroblasts (HFF) and protected these cells from an otherwise lethal combination of the S-phase drugs β-cytosine arabinoside and hydroxyurea. In contrast, HeLa cells continued cell cycle transit in the presence of histidinol and theophylline. Consequently, these reagents did not alter the vulnerability of HeLa cells to combined S-phase drugs. The differential S-phase drug sensitivity mediated by histidinol and theophylline persisted under cocultivation conditions, thereby allowing the selective and total eradication of colonies of HeLa cells in the presence of subconfluent HFF cells. The HFF cells, spared S-phase drug toxicity by their unique response to histidinol and theophylline, showed total survival and viability.