Τίτλος:
Lack of association between GSTT1 polymorphism and endogenous or
benzo[a]pyrene-induced sister chromatid exchanges as analyzed in
metaphase or G2-phase lymphocytes
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The objectives of the present work are (1) to verify whether genetic
polymorphism in the detoxification gene GSTT1 influences the endogenous
sensitivity in terms of sister chromatid exchanges (SCEs)/cell in
healthy donors and (2) to test whether in vitro exposure to B[a]P in
terms of SCEs/cell can be associated with polymorphism of GSTT1 gene.
The presence or absence of the homozygous deletion in GSTT1 gene was
determined in peripheral blood cells using multiplex-PCR. For SCEs
quantitation, the cytogenetic method used thus far is based on the
analysis in metaphase chromosomes. Consequently, G2-arrested cells are
not included in the analysis. To overcome this shortcoming of the
conventional method, we applied here SCE analysis in G2-phase
prematurely condensed chromosomes (G2-PCCs) induced by calyculin-A,
using a modified fluorescence-plus-Giemsa staining protocol. Compared to
metaphase, a statistically significant increase in the yield of SCEs was
notified in the G2-phase analysis after 48 h exposure of peripheral
blood lymphocytes to 0.01-1 mM B[a]P, in both GSTT1-positive and -null
donors. Therefore, the analysis of SCEs in the G2-phase using
calyculin-A induced PCC methodology was shown to be more sensitive
compared to the analysis at the metaphase level. Nevertheless, the
results obtained do not show an association between the GSTT1
polymorphism with increased endogenous and/or B[a]P-induced
SCE-frequencies in peripheral blood lymphocyte chromosomes in vitro.
These results highlight not only the effect of B[a]P on cell cycle
kinetics but also they demonstrate that conventional cytogenetic
analysis at metaphase underestimates the cytogenetic effects of
chemicals that delay cell cycle progression in G2-phase.
Συγγραφείς:
Hatzi, V. I.
Terzoudi, G. I.
Stavropoulou, C.
Malik, S. I.
and Makropoulos, V.
Pantelias, G. E.
Περιοδικό:
Current Molecular Biology Reports
Λέξεις-κλειδιά:
Polymorphisms; GSTT1; SCEs; Genotoxicity; Cytogenetics; Toxicology
DOI:
10.1007/s11033-010-0513-4