TY - JOUR
TI - Interactions between CYP1A1 polymorphisms and exposure to environmental
tobacco smoke in the modulation of lymphocyte bulky DNA adducts and
chromosomal aberrations
AU - Georgiadis, P
AU - Topinka, J
AU - Vlachodimitropoulos, D
AU - Stoikidou, M
AU - and Gioka, M
AU - Stephanou, G
AU - Autrup, H
AU - Demopoulos, NA and
AU - Katsouyanni, K
AU - Sram, R
AU - Kyrtopoulos, SA
JO - Journal of Carcinogenesis
PY - 2005
VL - 26
TODO - 1
SP - 93-101
PB - Oxford University Press
SN - 1477-3163
TODO - 10.1093/carcin/bgh294
TODO - null
TODO - CYP1A1 plays an important role in the metabolic activation of polycyclic
aromatic hydrocarbons (PAH), carcinogenic components of air pollution.
The influence of CYP1A1 genotype ((*)2A, (*)2B and (*)4) on the
levels of lymphocyte bulky DNA adducts and the frequency of cells with
aberrant chromosomes was assessed in 194 non-smoking subjects in whom
recent exposure to environmental tobacco smoke (ETS) and airborne
particulate-associated PAH were measured during two consecutive seasons
(winter and summer). While CYP1A1(*)4 had no consistent effect on
either biomarker of genetic damage, the levels of both biomarkers
responded in a parallel fashion to changes in exposure/CYP1A1(*)2A
genotype combinations during both seasons. Specifically, the levels of
both biomarkers were increased in carriers of at least one CYP1A1(*)2A
allele, as compared with CYP1A1(*)1 homozygotes, in subjects with ETS
exposures >0.8 h/day during the previous 4 days and mean personal
exposure to benzo[a]pyrene <0.9 ng/m(3) during the previous 24 h (all
P < 0.05). Outside these exposure limits the differential effect in
CYP1A1(*)2A variants was lost. Although the numbers of subjects with
the CYP1A1(*)2B polymorphism was small, the same trend appeared to be
followed in this case. These effects are interpreted as resulting from
differential induction of CYP1A1 expression in CYP1A1(*)2A and
CYP1A1(*)2A/(*)2B carriers by components of ETS-polluted air at
levels of exposure readily suffered by large segments of the general
population and suggest that subjects with these genotypes may have
increased susceptibility to the genotoxic effects of ETS.
ER -