Absence of p53-mediated G1 arrest with induction of MDM2 in sterigmatocystin-treated cells

P53 plays a critical role in G1 checkpoint after DNA damage. MDM2 gene is a p53 target gene and its protein forms a feedback loop with p53 and inhibit s p53-mediated G1 arrest. Sterigmatocystin (ST) is a mycotoxin and carcinog en. In this study we show that exposure of cells to ST for 12 or 24 h resul ted in failure of G1 arrest at both time points. Accordingly, p53 protein w as not increased and p21WAF1 expression was inhibited at 12 h, and both pro teins were weakly induced at 24 h after treatment with ST. Meanwhile, MDM2 protein was induced in a p53 dependent fashion by ST at both 12 and 24 h. T he induction of MDM2 was coincident with the cellular responses of p53 and p21WAF1, and might contribute to the failure of G1 arrest in ST-treated cel ls. In addition, ST-treated cells exhibited G2M arrest, regardless of p53 s tatus. Our results indicate that the carcinogenic effects of ST seem to be mediated by failure of p53-mediated G1 checkpoint.