Gene and protein expressions in human cord blood cells after exposure to acrylonitrile.
Acrylonitrile is a very high volume industrial chemical used primarily in the manufacture of plastics and rubber, which displays a pronounced acute toxicity and may be carcinogenic. The damage to the hematopoietic function by acrylonitrile may result from interference with cytokine production and cytokine receptor binding. Our present data show that acrylonitrile modulates the expression of some genes implicated in cell differentiation, cell-cycle progression, and clonogenic potential of human cord blood cells. A macroarray hybridization analysis showed that expression of the CXCR4, MCP-1, and MRP8 genes was modified by acrylonitrile exposure. Moreover, the acrylonitrile cell target seems to be the myeloid compartment, as assessed by a CFU-GM assay. In particular, the downregulation of CXCR4, MCP1, and MRP8 can be responsible for the observed reduction of cell proliferation and clonogenic capability of CFU-GM precursors. A Western blot assay showed an acrylonitrile-dependent induction of Bax, while Bcl-2 expression changed only after 48 h of chemical exposure. Bax was overexpressed in respect to Bcl-2, and this fact can be responsible for the induction in cell death after 24 h of treatment. C-fos and c-jun were also downregulated after 24 h and 6 h of treatment, respectively.
Diodovich
Cristina
C
Laboratory of Hematotoxicology, ECVAM, Institute for Health and Consumer Protection, JRC, Ispra 21020, Italy.
Malerba
Ilaria
I
Ferrario
Daniele
D
Bowe
Gerard
G
Bianchi
Marco Giorgio
MG
Acquati
Francesco
F
Taramelli
Roberto
R
Parent-Massin
Dominique
D
Gribaldo
Laura
L
D000181:Acrylonitrile / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods
D002273:Carcinogens; D000181:Acrylonitrile