Different G2/M accumulation in M059J and M059K cells after exposure to DNA double-strand break-inducing agents.
OBJECTIVE
To investigate and compare the cell cycle progression in relation to cell death in the human glioma cell lines, M059J and M059K, after exposure to DNA double-strand break-inducing agents.


METHODS
The M059J and M059K cells, deficient and proficient in the catalytic subunit of the DNA-dependent protein kinase, respectively, were exposed to 1 and 4 Gy of photons or accelerated nitrogen ions. In addition, M059J and M059K cells were treated with 10 and 40 mug/mL of bleomycin for 30 min, respectively. Cell cycle progression, monitored by DNA flow cytometry, was measured up to 72 h after treatment.


RESULTS
M059J, but not M059K, cells displayed G(2)/M accumulation after low linear energy transfer irradiation. High linear energy transfer radiation exposure however, resulted in a substantial increase of M059K cells in the G(2)/M phase detected at 48 h. At 72 h, the number of cells in the G(2)/M phase was equivalent to its control. M059J cells accumulated mainly in S phase after high linear energy transfer irradiation. In contrast to M059K, M059J cells were still blocked at 72 h. Bleomycin induced G(2)/M accumulation for both M059J and M059K cells detected 24 h after treatment. At 48 h, the percentage of bleomycin-treated M059J cells in G(2)/M phase remained high, and the number of M059K cells had decreased to control levels. Neither cell line showed cell cycle arrest (< or =10 h) after exposure to these agents.


CONCLUSIONS
Distinct cell cycle block and release is dependent on the complexity of the induced DNA damage and the presence of the DNA-dependent protein kinase catalytic subunit.
Holgersson
Asa
A
Department of Oncology-Pathology, Unit of Medical Radiation Biology, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
Heiden
Thomas
T
Castro
Juan
J
Edgren
Margareta R
MR
Lewensohn
Rolf
R
Meijer
Annelie E
AE
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000378:metabolism; D016195:G2 Phase / Q000502:physiology; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D018499:Linear Energy Transfer; D008938:Mitosis / Q000502:physiology; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D001761:Bleomycin; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases