The benzene metabolite hydroquinone enhances G2-chromosomal radiosensitivity by inducing a less-efficient G2-M-checkpoint in irradiated lymphocytes.
The hypothesis tested is that a 24-h pre-irradiation-exposure of peripheral blood lymphocytes (PBL) to the benzene metabolite hydroquinone (HQ), at doses that are non-acutely toxic (5 microM), induces a less efficient G2-M-checkpoint and enhances the G2-chromosomal radiosensitivity in a statistically significant manner (p<0.01). A less efficient G2-M-checkpoint may allow the transition of damaged cells from G2- to M-phase and experimental data in the present work support this hypothesis. In fact HQ sensitizes lymphocytes obtained from healthy donors, as they exhibit increased G2-chromosomal radiosensitivity which interestingly is similar to that observed in cases of radiosensitive cancer-prone individuals. This finding is important since a deficiency in cell cycle checkpoints and an increase in G2-chromosomal radiosensitivity are linked to chromosomal instability, cancer proneness and the development of leukemia. The observed chromosome radiosensitization may be a consequence either of an effect of HQ on the initial induction of radiation-induced chromosomal aberrations, or on the DNA repair capacity of the cells, or it may be linked to HQ-induced alterations in the cell cycle and feedback control mechanism during the G2- to M-phase transition. In order to elucidate which is the mechanism involved, conventional cytogenetics and premature chromosome condensation (PCC) methodologies were applied. The experimental data obtained support the hypothesis that HQ increases G2-chromosomal radiosensitivity in human peripheral blood lymphocytes by inducing a less efficient G2-M-checkpoint, facilitating thus the transition of damaged cells from G2- to M-phase.
Hatzi
Vasiliki I
VI
Institute of Nuclear Technology and Radiation Protection, National Center for Scientific Research, NCSR Demokritos, Athens, Greece.
Terzoudi
Georgia I
GI
Pantelias
Gabriel E
GE
Spiliopoulou
Chara
C
Makropoulos
Vasilios
V
D001554:Benzene / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D016195:G2 Phase / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D006873:Hydroquinones / Q000633:toxicity*; D007621:Karyotyping; D008214:Lymphocytes / Q000187:drug effects / Q000528:radiation effects; D008387:Marine Toxins; D010080:Oxazoles / Q000633:toxicity; D011836:Radiation Tolerance / Q000187:drug effects*
D002273:Carcinogens; D006873:Hydroquinones; D008387:Marine Toxins; D010080:Oxazoles; C059041:calyculin A; D001554:Benzene; C031927:hydroquinone