Radiation could induce p53-independent and cell cycle--unrelated apoptosis in 5-fluorouracil radiosensitized head and neck carcinoma cells.
The effect of chemoresistance induction in radiosensitivity and cellular behavior after irradiation remains misunderstood. This study was designed to understand the relationship between radiation-induced cell cycle arrest, apoptosis, and radiosensitivity in KB cell line and KB3 subline selected after 5-fluorouracil (5FU) exposure. Exposure of KB cells to 5FU led to an increase in radiosensitivity. G2/M cell cycle arrest was observed in the two cell lines after irradiation. The radioresistant KB cell line reached the maximum arrest two hours before KB3. The cellular exit from this arrest was found to be related to the wild type p53 protein expression induction. After irradiation, only KB3 cell line underwent apoptosis. This apoptosis induction seemed to be independent of G2/M arrest exit, which was carried out later. The difference in radiosensitivity between KB and KB3 subline may result therefore from both a difference in apoptosis induction and a difference in G2/M arrest maximum duration. Moreover, 5FU exposure has led to an increase in constitutive p53 protein expression, which may be associated with an increase in basal apoptosis cell fraction. Given the existing correlation between radiosensitivity and the percentage of basal apoptosis, the constitutive p53 protein expression may be related to intrinsic radiosensitivity in our cellular model.
Centre Alexis Vautrin, Laboratoire de Recherche en Oncologie, Vandoeuvre-lès-Nancy, France.
C
C
Didelot
J F
JF
Mirjolet
M
M
Barberi-Heyob
C
C
Ramacci
J L
JL
Merlin
D017304:Annexin A5 / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D004396:Coloring Agents; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D005472:Fluorouracil / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D016158:Genes, p53 / Q000502:physiology*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D006801:Humans; D007624:KB Cells; D008938:Mitosis / Q000187:drug effects / Q000528:radiation effects; D011419:Propidium; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D017304:Annexin A5; D000964:Antimetabolites, Antineoplastic; D004396:Coloring Agents; D005456:Fluorescent Dyes; D011838:Radiation-Sensitizing Agents; D011419:Propidium; D016650:Fluorescein-5-isothiocyanate; D005472:Fluorouracil