DNA repair and cyclin D1 polymorphisms and styrene-induced genotoxicity and immunotoxicity.
1-SO-adenine DNA adducts, DNA single-strand breaks (SBs), chromosomal aberrations (CAs), mutant frequency (MF) at the HPRT gene, and immune parameters (hematological and of humoral immunity) were studied in styrene-exposed human subjects and controls. Results were correlated with genetic polymorphisms in DNA repair genes (XPD, exon 23, XPG, exon 15, XPC, exon 15, XRCC1, exon 10, XRCC3, exon 7) and cell cycle gene cyclin D1. Results for biomarkers of genotoxicity after stratification for the different DNA repair genetic polymorphisms showed that the polymorphism in exon 23 of the XPD gene modulates levels of chromosomal and DNA damage, HPRT MF, and moderately affects DNA adduct levels. The highest levels of biomarkers were associated with the wild-type homozygous AA genotype. The exposed individuals with the wild-type GG genotype for XRCC1 gene exhibited the lowest CA frequencies, compared to those with an A allele (P < 0.05). Cyclin D1 polymorphism seems to modulate the number of leukocytes and lymphocytes in the analyzed subjects. The number of eosinophiles was positively associated with XPD variant C allele and negatively with XRCC1 variant A allele (P < 0.05) and XPC variant C allele (P < 0.05). Immunoglobulin IgA was positively associated with an XRCC3 variant T allele (P < 0.01) and negatively with XPC variant C allele (P < 0.05). Both C3- and C4-complement components were lower in individuals with XRCC3 CT (P < 0.05) and TT genotypes (P < 0.01). Adhesion molecules sL-selectin and sICAM-1 were associated with XPC genotype (P < 0.05). Individual susceptibility may be reflected in genotoxic and immunotoxic responses to environmental and occupational exposures to xenobiotics.
Department of Genetic and Molecular Toxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic.
M
M
Kuricova
A
A
Naccarati
R
R
Kumar
M
M
Koskinen
S
S
Sanyal
M
M
Dusinska
J
J
Tulinska
L
L
Vodickova
A
A
Liskova
E
E
Jahnova
L
L
Fuortes
V
V
Haufroid
K
K
Hemminki
P
P
Vodicka
D000328:Adult; D019938:Cyclin D1 / Q000235:genetics*; D004260:DNA Repair; D005260:Female; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009153:Mutagens / Q000633:toxicity*; D016273:Occupational Exposure; D011110:Polymorphism, Genetic; D020058:Styrene / Q000633:toxicity*
D009153:Mutagens; D019938:Cyclin D1; D020058:Styrene