Interactions between CYP1A1 polymorphisms and exposure to environmental tobacco smoke in the modulation of lymphocyte bulky DNA adducts and chromosomal aberrations.
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/m3 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.
National Hellenic Research Foundation, Institute of Biological Research and Biotechnology, 48 Vas Constantinou Avenue, Athens 116 35, Greece. panos@eie.gr
Panagiotis
P
Georgiadis
Jan
J
Topinka
Dimitris
D
Vlachodimitropoulos
Melpomeni
M
Stoikidou
Maria
M
Gioka
Georgia
G
Stephanou
Herman
H
Autrup
Nikolaos A
NA
Demopoulos
Klea
K
Katsouyanni
Radim
R
Sram
Soterios A
SA
Kyrtopoulos
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002869:Chromosome Aberrations; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D018736:DNA Adducts; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D011110:Polymorphism, Genetic; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D015415:Biomarkers; D018736:DNA Adducts; D014028:Tobacco Smoke Pollution; D019363:Cytochrome P-450 CYP1A1