Lack of uncoupling of S phase and mitosis after irradiation in p53- human lymphoblast cell lines.
It has been shown that p53- human colorectal cancer cells arrest after DNA damage in a G2-like state and may then undergo DNA synthesis without intervening mitosis (Waldman et al., Nature 381, 713-716, 1996). To further clarify the role of p53 in the regulation of the G2/M-phase checkpoint, we have studied cells of three closely related human lymphoblastoid cell lines (TK6, WTK1 and TK6E6, an HPV16 E6-transfected TK6 line) with differing p53 status. The cells were irradiated with 1.5-12 Gy gamma rays with or without 2 mM caffeine. There was no evidence of uncoupling of DNA synthesis and mitosis after irradiation in the p53- cell lines, WTK1 and TK6E6, suggesting that this uncoupling may not be a universal phenomenon. The apparent formation of tetraploid cells after irradiation of cells of the p53- WTK1 line was due to the occurrence of a G2-phase block in a pre-existing tetraploid population. These results support the conclusion that control of the G2/M-phase checkpoint after irradiation may differ among different cell types.
Wenz
F
F
Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Yu
Y
Y
Nagasawa
H
H
Imrich
A C
AC
Keng
P
P
Little
J B
JB
D002110:Caffeine / Q000494:pharmacology; D002460:Cell Line; D004247:DNA / Q000032:analysis; D016195:G2 Phase; D006801:Humans; D008214:Lymphocytes; D008938:Mitosis / Q000528:radiation effects*; D016196:S Phase / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D016159:Tumor Suppressor Protein p53; D002110:Caffeine; D004247:DNA