The cytotoxic effect of E1B 55-kDa mutant adenovirus on human hepatocellular carcinoma cell lines

It has been suggested the E1 B 55 kDa mutant adenovirus dl1520 can selectiv ely kill p53-deficient human tumor cells. In this study, we examined the cy totoxic effect of dl1520 on nine human hepatocellular carcinoma (HCC) cell lines with different p53 genetic and functional status. The results showed that HCC cell lines with deleted or mutant p53 gene and reduced p53 transcr iptional activities were more susceptible to dl1520-induced cytolysis. Hep3 B (p53-null) and HepG2 (p53-wt) cells were arrested at G2/M phase when cyto lysis occurred. Cyclin-dependent kinase inhibitor (CDKI) p21(Waf-1/Cip-1) w as downregulated 24 hours after dl1520 infection in HepG2 cells and increas ed when cytolysis occurred. No p21 expression was detected in Hep3B cells. DNA fragmentation was found in both Hep3B and HepG2 cells after dl1520 infe ction. Bax expression increased in dl1520-infected HepG2 cells but not in H ep3B cells. Notably, three Bax-like proteins, molecular mass around 40 to 8 0 kDa, accumulated 48 hours after adenovirus infection in Hep3B cells but n ot in HepG2 cells. These results suggest that the susceptibility of HCC cel ls to dl1520- induced cytolysis is related to both p53 genotype and functio nal status, and is mediated by both cell cycle disturbance and apoptosis.