Role of haemoglobin in the protection of cultured lymphocytes against diepoxybutane (DEB), assessed by in vitro induced chromosome breakage.
Diepoxybutane (DEB) is an alkylating agent that can be used to assess chromosome instability in repair-deficient subjects. Previous authors investigated the role of red blood cells (RBC) in determining individual susceptibility to DEB in normal healthy donors, and demonstrated that a polymorphic enzyme in RBC, Glutathione S-transferase T1 (GSTT1), is involved in DEB detoxification. In the present work we studied the influence of individual GSTM1 and GSTT1 genotypes and the presence of RBC on the frequency of DEB-induced chromosome breakage in lymphocyte cultures from normal individuals and, in particular, the influence of isolated components of RBC: RBC membranes, RBC lysate, and haemoglobin. Our results confirm that individual GSTT1 genotypes modulate the level of genetic lesions induced by DEB; however, this effect was not sufficient to explain the highly significant variation in chromosome breakage between whole blood and RBC-depleted cultures. We showed that RBC can protect cultured lymphocytes against chromosome breakage induced by DEB and we demonstrated the particular role of haemoglobin in the protective effect.
Porto
Beatriz
B
Laboratory of Cytogenetics, Instituto Ciências Biomédicas Abel Salazar (ICBAS), Largo do Prof. Abel Salazar, No. 2, 4099-003, Porto, Portugal.
Chiecchio
Laura
L
Gaspar
Jorge
J
Faber
Ana
A
Pinho
Luciana
L
Rueff
José
J
Malheiro
Isabel
I
D000328:Adult; D002478:Cells, Cultured; D019457:Chromosome Breakage; D002877:Chromosomes, Human / Q000187:drug effects*; D019610:Cytoprotection / Q000502:physiology; D004249:DNA Damage / Q000235:genetics; D004852:Epoxy Compounds / Q000633:toxicity*; D004912:Erythrocytes / Q000502:physiology; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics; D006454:Hemoglobins / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009153:Mutagens / Q000633:toxicity*
D004852:Epoxy Compounds; D005982:Glutathione Transferase; D006454:Hemoglobins; D009153:Mutagens; C007366:diepoxybutane; C413545:glutathione S-transferase T1