Probing lethal damage expression in cytochalasin B-induced polykaryons by radiation quality.
The polykaryon-forming unit (PFU) cell survival assay is based on the postirradiation flow cytometric analysis of the DNA content accumulated in high-ploidy cells (polykaryons) induced by the cytokinesis inhibitor cytochalasin B and can provide a meaningful measure of cell radiosensitivity. In this assay, cell survival is defined as the ability to form a polykaryon of a given ploidy after irradiation. The slope of the polykaryon dose response has been shown to be highly correlated with the initial slope of the clonogenic survival curves after gamma irradiation, which implies a common subset of lethal lesions. We reported previously on an apoptotic mode of cell death in the polykaryon system and on the heritability of small variations in polykaryon radioresponse. We now show that exposure of PFUs to a given dose of alpha particles results in a greater reduction in the proportion of cells able to reach at least 16C when compared to the same dose of low-LET radiation. This reduction is less than that observed in the low-dose (alpha term) region of the clonogenic curve. On the basis of published LET-dependent spectra of radiation-induced DNA damage, we suggest that this behavior reflects a differential expression of lethal damage that can be probed by varying the LET of the radiation and that base damages contributing additional complexity to clustered DNA lesions may be more deleterious in PFUs than in clonogens.
Department of Physical Sciences, Radiation Biophysics Laboratory, University of Naples Federico II, Italy. manti@na.infn.it
Lorenzo
L
Manti
Ifor Delme
ID
Bowen
David Lucas
DL
Stevens
Jonathan Bradley
JB
Court
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D003571:Cytochalasin B / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects* / Q000528:radiation effects*; D015870:Gene Expression / Q000187:drug effects* / Q000528:radiation effects*; D011003:Ploidies
D003571:Cytochalasin B