Cell cycle arrest and aberration yield in normal human fibroblasts. II: Effects of 11 MeV u-1 C ions and 9.9 MeV u-1 Ni ions.
OBJECTIVE
To investigate further the relationship between high linear energy transfer (LET) induced cell cycle arrests and the yield of chromosome aberrations observable in normal human fibroblasts at the first post-irradiation mitosis.


METHODS
Normal human fibroblasts (AG01,522C) were exposed in G0/G1 to either 11 MeV u(-1) C ions (LET = 153.5 keV microm(-1)) or 9.9 MeV u(-1) Ni ions (LET = 2,455 keV microm(-1)), subcultured in medium containing 5-Bromo-2'-deoxyuridine (BrdU) and at multiple time-points post-irradiation the yield of chromosomal damage, the mitotic index and the cumulative BrdU-labelling index were determined. Furthermore, a mathematical approach was used to analyse the entire cell population.


RESULTS
Following high LET exposure normal fibroblasts suffer a transient delay into S-phase and into mitosis as well as a prolonged, probably permanent cell cycle arrest in the initial G0/G1-phase. Cells that reach the first mitosis at early times carried less aberrations than those collected at later times indicating a relationship between cell cycle delay and the number of aberrations. However, with respect to the whole cell population, only a few aberrant fibroblasts are able to progress to the first mitosis. For all endpoints studied the relative biological effectiveness (RBE) of C ions is in the range of 2 - 4, while for Ni ions RBE < 1 is estimated. In contrast, when compared on a per particle basis Ni ions with the higher ionization density were found to be more effective.


CONCLUSIONS
Detailed analysis of the data demonstrates that the number of fibroblasts at risk for neoplastic transformation is significantly reduced by a chronic cell cycle arrest in the initial G0/G1-phase and, for the first time, the LET-dependence of this effect has been shown.
Tenhumberg
S
S
Biophysik, Gesellschaft für Schwerionenforschung, Darmstadt, Germany.
Gudowska-Nowak
E
E
Nasonova
E
E
Ritter
S
S
D001973:Bromodeoxyuridine / Q000494:pharmacology; D002244:Carbon / Q000737:chemistry; D002453:Cell Cycle / Q000528:radiation effects*; D016923:Cell Death / Q000528:radiation effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000166:cytology / Q000528:radiation effects*; D016193:G1 Phase / Q000528:radiation effects; D006801:Humans; D007477:Ions / Q000737:chemistry*; D018499:Linear Energy Transfer; D008938:Mitosis / Q000528:radiation effects*; D009532:Nickel / Q000737:chemistry; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D012062:Relative Biological Effectiveness; D016192:Resting Phase, Cell Cycle / Q000528:radiation effects; D013997:Time Factors
D007477:Ions; D011838:Radiation-Sensitizing Agents; D002244:Carbon; D009532:Nickel; D001973:Bromodeoxyuridine