Gamma-irradiation does not impair ATRA-induced maturation of myeloid leukaemic cells: implication for combined radiation and differentiation therapy.
In the present study we investigated the effects of various doses of gamma-irradiation, followed by induction of granulocytic differentiation with all-trans-retinoic acid (ATRA), on proliferative rate, differentiation capability and oxidative metabolism of leukaemic cells from two different myeloid leukaemia cell lines, HL-60 and PLB-985. Regarding the effects of such combined treatment on the proliferative capabilities of HL-60 and PLB-985 cell lines, we showed that their growth kinetics were similar after 2 Gy gamma-irradiation combined with ATRA. However, with doses >2 Gy, the behaviour of the cell lines differed largely. Indeed, HL-60 appeared to be more radiosensitive than PLB-985 regarding cell viability and proliferation. Besides, whatever dose of irradiation (2, 5 or 10 Gy) was applied, ATRA was still able to induce differentiation of HL-60 and PLB-985 into granulocytes that retained the capacity to produce superoxide anion. The results of these in vitro studies suggest that leukaemia cell lines retain their ability to respond to ATRA, a granulocytic-differentiating inducer following high doses of irradiation. This may have implications for the use of radiation therapy in combination with ATRA for the treatment of extramedullary infiltrations of myeloid leukaemias in humans.
Neildez-Nguyen
T M
TM
Institut de Protection et de Sûreté Nucléaire, Département de Protection de la Santé de l'Homme et de Dosimétrie, IPSN, Fóntenay-aux-Roses, France.
Chapel
A
A
Arock
M
M
Vétillard
J
J
Thierry
D
D
D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D005720:Gamma Rays / Q000627:therapeutic use*; D018922:HL-60 Cells; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000532:radiotherapy*; D014212:Tretinoin / Q000627:therapeutic use*
D014212:Tretinoin