Acrylonitrile exposure: the effect on p53 and p21(WAF1) protein levels in the blood plasma of occupationally exposed workers and in vitro in human diploid lung fibroblasts.
Acrylonitrile (ACN) is a compound widely used in the synthesis of a variety of organic products. It has been found that ACN is carcinogenic in rats, and some epidemiological studies also suggest a possible carcinogenic effect of ACN in humans. The aim of the present study was to assess the effect of ACN exposure on the expression of p53 and p21(WAF1) proteins in vitro as well as in vivo. In vitro ACN exposure of human lung fibroblasts resulted in the induction of both p53 and p21(WAF1) proteins. To evaluate the effect of ACN on the levels of p53 and p21(WAF1) proteins in the blood plasma of ACN-exposed workers, samples from 49 subjects (average age 44 years, 88% males, 12% females) exposed to ACN in the petrochemical industry (ACN concentration ranged from 0.05 to 0.3mg/m(3)) were analyzed. Subjects living in the same area (N=24, average age 43 years, 92% males, 8% females), but not working in the petrochemical industry were used as controls. No significant differences in either p53, or p21(WAF1) levels between the exposed and control groups were found. The expression of p53 was significantly higher in exposed non-smokers as compared with smokers (P=0.02). No effect of GSTM1 and GSTT1 genotypes on the expression of either protein was observed. Subjects with an EPHX high activity genotype had significantly higher p21(WAF1) expression as compared with genotypes with low or medium EPHX activity. We conclude that plasma levels of both proteins are not relevant biomarkers for occupational ACN exposure.
Rössner
Pavel
P
Laboratory of Genetic Ecotoxicology, Regional Institute of Hygiene of Central Bohemia and Institute of Experimental Medicine AS CR, Vídenská 1083, 142 20 Prague 4, Czech Republic. rossner@biomed.cas.cz
Binková
Blanka
B
Chvátalová
Irena
I
Srám
Radim J
RJ
D000181:Acrylonitrile; D000328:Adult; D015153:Blotting, Western; D002273:Carcinogens; D002478:Cells, Cultured; D003367:Cotinine / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D000181:Acrylonitrile; D002273:Carcinogens; D003367:Cotinine; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D005982:Glutathione Transferase; D016159:Tumor Suppressor Protein p53; C493956:CDKN1A protein, human; C413545:glutathione S-transferase T1