DNA as an important target in radiation-induced apoptosis of MYC and MYC plus RAS transfected rat embryo fibroblasts.
OBJECTIVE
This study uses a radiation chemistry approach to determine if DNA is an important target for radiation-induced apoptosis of myc (MR4) and myc plus ras (3.7) transfected rat embryo fibroblast cell lines.


METHODS
The radiation protection efficiency of four thiols was compared with net molecular charge ranging from -1 to +2: mercaptopropionic acid (Z= -1), mercaptoethanol (Z=0), cysteamine (Z= +1), N(2-mercaptoethyl)-1,3-diaminopropane (Z= +2). Protection factors were determined for these thiols against radiation-induced apoptosis (Apoalert assay), mitotic cell death (clonogenic assay) and double-strand break (dsb) induction (pulse field gel electrophoresis) in MR4 and 3.7 cells. Theoretical protection factors for these thiols against dsb induction were also calculated from second-order chemical repair constants for single-strand breaks (ssb) and the concentration of added thiols in MR4 and 3.7 cell lines.


RESULTS
The charge-dependent increases observed for measured protection factors against radiation-induced apoptosis did not differ significantly between the two cell lines, nor did they differ significantly from the corresponding increases observed for radiation-induced mitotic cell killing and for induction of dsb. The calculated protection factor for dsb also showed a thiol charge-dependent increase similar to the measured protection factors for all of the other parameters studied.


CONCLUSIONS
These results are consistent with the hypothesis that DNA is an important target for radiation-induced apoptosis.
Ayene
I S
IS
University of Pennsylvania School of Medicine, Department of Radiation Oncology, Philadelphia 19104-6072, USA. ayenei@mail.med.upenn.edu
Bernhard
E J
EJ
McKenna
W G
WG
Muschel
R J
RJ
Krisch
R E
RE
Koch
C J
CJ
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003114:Colony-Forming Units Assay; D019610:Cytoprotection / Q000187:drug effects; D004247:DNA / Q000378:metabolism / Q000528:radiation effects*; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D016166:Free Radical Scavengers / Q000378:metabolism / Q000494:pharmacology; D016259:Genes, myc / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D007424:Intracellular Fluid / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology; D051381:Rats; D013438:Sulfhydryl Compounds / Q000493:pharmacokinetics / Q000494:pharmacology; D014162:Transfection
D016166:Free Radical Scavengers; D011837:Radiation-Protective Agents; D013438:Sulfhydryl Compounds; D004247:DNA