Specific chromosome instability induced by heavy ions: a step towards transformation of human fibroblasts?
Cultures of human skin fibroblasts were exposed to heavy ions: neon (E = 10.74 MeV/u) and argon (E = 10.52 MeV/u) at fluences of 10(6), 2 x 10(6) and 4 x 10(6) and lead (E = 9.5 MeV/u) at a fluence of 2 x 10(6) particles/cm2. Cultures were further prolonged for up to 25 passages and karyotyping was performed at various times. Radiation-induced chromosome anomalies progressively decreased, became quite rare at passages 5-7 and increased at later passages. Around passages 20-25, most anomalies occurring were dicentrics, involving telomeric regions of 13p and q arms principally and to a lesser degree those of 1p, 16p and 16q arms. These non-random rearrangements paralleled the appearance of clones with unbalanced karyotypes. In particular, two independent proliferating clones were characterized by a monosomy 13. It is concluded that most chromosome lesions directly induced by heavy ions are hardly compatible with cell survival and thus disappear after a few cell generations. However, surviving cells acquire a de novo chromosome instability leading to the formation of clones with unbalanced karyotypes at late passages.
Martins
M B
MB
Commissariat à l'Energie Atomique, DSV/DPTE/LCG, Fontenay-aux-Roses, France.
Sabatier
L
L
Ricoul
M
M
Pinton
A
A
Dutrillaux
B
B
D001128:Argon / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002648:Child; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000528:radiation effects*; D004735:Energy Transfer; D005347:Fibroblasts; D006801:Humans; D007621:Karyotyping; D007854:Lead / Q000494:pharmacology*; D008677:Metaphase; D009356:Neon / Q000494:pharmacology*
D007854:Lead; D009356:Neon; D001128:Argon