Abrogation of p53 function by HPV16 E6 gene delays apoptosis and enhances mutagenesis but does not alter radiosensitivity in TK6 human lymphoblast cells.
In order to gain a better understanding of the role of p53 in radiation-induced mitotic failure, apoptosis and mutagenesis, we introduced the HPV16 E6 gene via a retroviral vector into the TK6 human lymphoblast cell line which expresses wild type p53. Abrogation of p53 function by E6 resulted in a delayed and reduced apoptotic response and a moderate increase in the frequency of mutations at the thymidine kinase (tk) locus following gamma-irradiation, but failed to alter radiosensitivity. The apoptotic response of the E6-transduced line was intermediate between that of wild type TK6 and the WTK1 cell line. WTK1 is derived from the same parental cell line as TK6 but expresses mutant p53. The spontaneous and gamma-ray-induced mutation frequencies in E6-transduced TK6 cells, although higher than that of the parental TK6 cell line, were still much lower than that of the WTK1 line. No effect on apoptosis, radiosensitivity or mutability was observed when the HPV16 E6 gene was introduced into the WTK1 cells. These results indicate that p53 does not regulate the radiosensitivity of TK6 cells through the apoptotic pathway. Furthermore, the previously observed enhanced radioresistance and mutability in WTK1 cells must be attributed to a more complex mechanism than p53 status alone.
Yu
Y
Y
Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Li
C Y
CY
Little
J B
JB
D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects*; D005720:Gamma Rays; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects*; D008297:Male; D016296:Mutagenesis; D009856:Oncogene Proteins, Viral / Q000494:pharmacology*; D012097:Repressor Proteins; D014161:Transduction, Genetic; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53