Pioneering reports by Suzuki and Ollis (1990) and Al-Rubeai et al. (1992) showing increased specific productivity of growth-inhibited hybridoma cells stimulated research on chemical culture additives to arrest cell growth and initiated efforts to control cell growth by controlled overexpression or inhibition of selected genes. Three successful one-gene metabolic engineering strategies have been developed to reversibly control mammalian cell growth: (i) estrogen-regulated overexpression of the interferon-responsive factor (IRF-1), a transcription factor which is upregulated by interferons as response to viral cell invasion, in BHK cells (Koester et al., 1995) ; (ii) dexamethasoneinducible suppression of the key transcription factor c-jun by antisense technology in Friend murine erythroleukemia cells (F-MEL) (Kim et al., 1998) ; and (iii) tetracycline-regulated overexpression of negative key regulators of the cell-cycle including the tumor suppressor p53 and the CDIs p21 and p27 in CHO cells (Fussenegger et al., 1997a; Fussenegger et al., 1998a and 1998b) . Overexpression of IRF-1 resulted in cell-cycle-independent growth arrest, but heterologous gene expression was not enhanced unless the exogenous genes were placed under control of IRF1-responsive promoters. Furthermore, IRF-1overexpressing BHK cells rapidly die, probably by an apoptosis-independent pathway (Koester et al., 1995; Müller et al., 1998) . On the contrary, c-jun suppression leads to sustained G0-phase arrest of F-MEL cells for over two weeks and protects these cells against apoptosis (Kim et al., 1998) . Unfortunately, this promising antisense technology remains to be assessed in an industrially relevant cell line and in connection with cloned protein production. However, G0-arrested cells have previously shown to produce exogenous protein at a lower rate (Kim et al., 1998) .