Sensitivity of human cord blood cells to tetrachloroethylene: cellular and molecular endpoints.
The International Agency for Research on Cancer (IARC) currently lists tetrachloroethylene [perchloroethylene (PCE)] as being carcinogenic in animals. PCE is listed as possibly carcinogenic to humans upon occupational exposure. Human exposure to PCE can produce oesophageal cancer, cervical cancer, non-Hodgkin's lymphoma, urinary bladder cancer and leukemia. This work shows that PCE modulates the expression of some genes implicated in cancer induction, cell differentiation, cell-cycle progression, and the survival and clonogenic potential of human cord blood cells. After exposure to the compound, the modulated genes were involved in inflammatory responses as with the mitogen-activated protein kinase 14 (MPK 14), or in tumor and metastasis progression as with the matrix metalloproteinase 17 (MMP 17), in cell proliferation as with c-jun and c-fos, and moreover in the apoptotic process as with interferon alpha-inducible protein (IFI), BAX and BCL-2. Analysis of cord blood cells via flow cytometry showed that PCE treatment induced a statistically significant increase in necrosis after 24 h, while the clonogenicity of Human Colony-Forming Unit-Granulocyte/Macrophage (CFU-GM) and Burst-Forming Unit-Erythrocyte (BFU-E) progenitors did not change. In conclusion, our data showed that PCE affected various pathways involved in cancer induction, but its action on cell proliferation and differentiation is not yet clearly understood.
Diodovich
Cristina
C
Laboratory of Hematotoxicology, ECVAM, Institute for Health and Consumer Protection, J.R.C., 21020 Ispra, Italy.
Ferrario
Daniele
D
Casati
Barbara
B
Malerba
Ilaria
I
Marafante
Erminio
E
Parent-Massin
Dominique
D
Gribaldo
Laura
L
D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D015672:Erythroid Precursor Cells / Q000187:drug effects; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry; D016147:Genes, Tumor Suppressor / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009369:Neoplasms / Q000139:chemically induced / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes / Q000187:drug effects / Q000235:genetics; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012997:Solvents / Q000633:toxicity*; D013750:Tetrachloroethylene / Q000633:toxicity*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation / Q000187:drug effects
D012997:Solvents; D013778:Tetrazolium Salts; D013844:Thiazoles; D012313:RNA; C022616:thiazolyl blue; D013750:Tetrachloroethylene