FUNCTIONAL EXPRESSION OF HUMAN P21(WAF1 CIP1) GENE IN RAT GLIOMA-CELLS SUPPRESSES TUMOR-GROWTH IN-VIVO AND INDUCES RADIOSENSITIVITY/

This study reports the successful growth suppression of a rat glioblas toma model (RT-2) both in vitro and in vivo by the insertion of p21(WA F1/CIP1), a negative cell cycle regulatory gene, into the tumor cells. Greater than 95% of the tumor cells expressed p21 protein after being infected with pCL based p21 retrovirus at 4x M.O.I. (multiplicity of infection), The pal-infected cells showed a 91% reduction in colony fo rming efficiency and a 66% reduction in growth rate, More prominent p2 1 staining was found in cells exhibiting histologic evidence of senesc ence. Intracranial implantation of the infected cells showed complete disappearance of the pal-infected cells at day 10 and long-term surviv al of the animals compared to controls. Injection of pCLp21 virus into tumor established in situ showed tumor necrosis and gene expression. In a clonogenic radiation survival assay, a 93% reduction of surviving colonies of pal-infected cells was seen in comparison to vector-infec ted control cells and to p53-infected cells after exposure to 8 Gy (80 0 rads). (C) 1997 Academic Press.