DNA damage, DNA repair rates and mRNA expression levels of cell cycle genes (TP53, p21(CDKN1A), BCL2 and BAX) with respect to occupational exposure to styrene.
We studied the relationship between DNA damage, DNA repair rates and messenger RNA (mRNA) expression levels of cell cycle genes TP53, p21(CDKN1A), BCL2 and BAX in a group of 71 styrene-exposed workers and 51 control individuals. The exposure was assessed by measuring the concentration of styrene at workplace and in blood. Parameters of DNA damage [measured as single-strand breaks (SSBs) and endonuclease III-sensitive sites], γ-irradiation-specific DNA repair rates and mRNA levels of studied genes were analyzed in peripheral blood lymphocytes. The workers were divided into low (<50 mg/m³) and high (>50 mg/m³) styrene exposure groups. We found negative correlations between mRNA expression of TP53, BCL2, BAX and styrene exposure (P < 0.001 for all parameters). In contrast, p21(CDKN1A) mRNA expression significantly increased with increasing styrene exposure (P = 0.001). SSBs and endonuclease III-sensitive sites increased with increasing mRNA levels of TP53 (P < 0.001 for both) and BCL2 (P = 0.038, P = 0.002, respectively), whereas the same parameters decreased with increasing mRNA levels of p21(CDKN1A) (P < 0.001, P = 0.007, respectively). γ-Irradiation-specific DNA repair rates increased with p21(CDKN1A) mRNA levels up to the low exposure level (P = 0.044). Our study suggests a possible relationship between styrene exposure, DNA damage and transcript levels of key cell cycle genes.
Hanova
Monika
M
Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of Czech Republic, Prague, Czech Republic.
Vodickova
Ludmila
L
Vaclavikova
Radka
R
Smerhovsky
Zdenek
Z
Stetina
Rudolf
R
Hlavac
Pavel
P
Naccarati
Alessio
A
Slyskova
Jana
J
Polakova
Veronika
V
Soucek
Pavel
P
Kumar
Rajiv
R
Hemminki
Kari
K
Vodicka
Pavel
P
D000328:Adult; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D018816:Genes, cdc / Q000187:drug effects*; D006801:Humans; D008297:Male; D016273:Occupational Exposure / Q000009:adverse effects*; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020058:Styrene / Q000009:adverse effects*; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000235:genetics
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D020058:Styrene