In another strategy, transient tetracycline-responsive overexpression of p53, p21 or p27 in a dicistronic configuration (SEAP-p53; SEAP-p21; SEAP-p27) led to G1-specific cell-cycle arrest, and in each case was accompanied by an up to 4-fold increase in SEAP production compared to proliferation-competent control cells (Fussenegger et al., 1997a) . These results compare favourably with those from G1-arrested, temperature-sensitive CHO cells generated by random mutagenesis, which also showed a 3-4-fold higher heterologous protein production upon growth arrest but retained low cell viability at elevated permissive temperatures (Jenkins and Hovey, 1993) .