Carcinogenesis Advance Access published online on September 30, 2004
Carcinogenesis, doi:10.1093/carcin/bgh294
© 2004 by Oxford University Press
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1 National Hellenic Research Foundation, Inst. of Biological Research and Biotechnology, 48, Vas Constantinou Av, Athens 116 35, Greece
* To whom correspondence should be addressed.
CYP1A1 plays an important role in the metabolic activation of polycyclic aromatic hydrocarbons (PAH), carcinogenic components of air pollution. The influence of CYP1A1 genotypes (*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 to CYP1A1*1 homozygotes, in subjects with ETS exposure exceeding 0.8 hours/day during the previous 4 days and mean personal exposure to benzo[a]pyrene below 0.9 ng/m3 during the previous 24 hours (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 also. 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.
Revised September 15, 2004
Accepted September 21, 2004
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Interactions between CYP1A1 polymorphisms and exposure to environmental tobacco smoke in the modulation of lymphocyte bulky DNA adducts and chromosomal aberrations
2 Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine Acad. Sci. C.R. and Health Institute of Hygiene of Central Bohemia, Videnska 1083, 142 20 Prague 4, Czech Republic
3 Division of Genetics, Cell and Developmental Biology, Department of Biology, University of Patras, 26100 Patras, Greece
4 Laboratory of Hygiene and Epidemiology, University of Athens Medical School, 115 27 Athens, Greece
5 Department of Environmental and Occupational Medicine, Univ. of Aarhus, Bldn. 180, DK-8000 Aarhus C, Denmark
6 National Hellenic Research Foundation, Inst. Of Biological Research and Biotechnology, 48, Vas Constantinou Av, Athens 116 35, Greece
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