The role of foetal red blood cells in protecting cultured lymphocytes against diepoxybutane-induced chromosome breaks.
Diepoxybutane (DEB) is an established mutagen that induces chromosome damage following in vitro treatment of peripheral blood lymphocytes. It is widely used to identify patients with Fanconi Anemia (FA), a clinical situation that is characterized, besides the hypersensitivity to DEB, by an elevated foetal haemoglobin (HbF) content in the peripheral blood. In a previous study, we showed that red blood cells (RBC) from normal individuals can protect cultured lymphocytes against chromosomal breaks induced by DEB and demonstrated the particular role of haemoglobin in the protective effect. In the present work, we studied the influence of RBC extracted from umbilical cord blood of neonates (F cells) on the frequency of DEB-induced chromosome breaks in lymphocyte cultures from normal individuals. Simultaneously, we determined individual GSTT1 and GSTM1 genotypes and the activity of Pi-class glutathione S-transferase (GSTP), catalase and superoxide dismutase (SOD) in adult and foetal RBC. Our results show that F cells, in comparison with adult RBC, elicit a better protection of cultured lymphocytes from normal individuals against chromosome breaks induced by DEB. Variability in the protective effect among RBC from different individuals was observed; we confirmed that the GSTT1 genotype modulates this inter-individual variability, but it is not sufficient to explain all of the protective effect of F cells. Our results suggest that the increased protective effect of F cells can be, at least in part, correlated with an increase in the activity of glutathione S-transferase, catalase and superoxide dismutase, in particular Cu/Zn SOD, in F cells compared with adult RBC.
Porto
Beatriz
B
Laboratory of Cytogenetics, ICBAS-Instituto Ciências Biomédicas Abel Salazar, Universidade do Porto, Largo do Prof, Abel Salazar, no. 2, 4099-003 Porto, Portugal. bporto@icbas.up.pt
Oliveira
Ricardo Jorge Dinis
RJ
Sousa
Carla
C
Gaspar
Jorge
J
Rueff
José
J
Carvalho
Félix
F
Malheiro
Isabel
I
D000328:Adult; D002273:Carcinogens / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D002450:Cell Communication; D002478:Cells, Cultured; D019457:Chromosome Breakage; D004852:Epoxy Compounds / Q000633:toxicity*; D004912:Erythrocytes / Q000502:physiology*; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D005333:Fetus / Q000502:physiology; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D013482:Superoxide Dismutase / Q000378:metabolism
D002273:Carcinogens; D004852:Epoxy Compounds; C007366:diepoxybutane; D002374:Catalase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase