Exposure of Tg.AC transgenic mice to benzene suppresses hematopoietic progenitor cells and alters gene expression in critical signaling pathways.
The effects of acute benzene (BZ) exposure on hematopoietic progenitor cells (HPCs) derived from bone marrow cells were studied using homozygous male v-Ha-ras Tg.AC mice at 8-10 weeks of age. The mice were given 0.02% BZ in their drinking water for 28 days with the dose rate estimated to be 34 mg benzene/kg BW/day. Analysis of cultured HPCs indicated that BZ suppressed the proliferation of the multilineage colony forming unit-granulocyte, erythrocyte, macrophage, megakaryocyte (CFU-GEMM); colony forming unit-granulocyte, macrophage (CFU-GM); and blast forming unit erythrocyte/colony forming unit erythrocyte (BFUE/CFUE). A gene expression profile was generated using nylon arrays spotted with 23 cDNAs involved in selected signal pathways involved in cell distress, inflammation, DNA damage, cell cycle arrest, and apoptosis. Of the 23 marker genes, 6 (bax, c-fos, E124, hsf1, ikBa, and p57) were significantly (Mann-Whitney U tests, P < 0.05) overexpressed in BZ-exposed mice. Two genes (c-myc and IL-2) approached significance (at P = 0.053). The pattern of gene expression was consistent with BZ toxicity and the suppression of HPCs.
Nwosu
Veronica C
VC
Department of Biology, North Carolina Central University, Durham, NC 27707, USA. vcnwosu@wpo.nccu.edu
Kissling
Grace E
GE
Trempus
Carol S
CS
Honeycutt
Hayden
H
French
John E
JE
D000818:Animals; D001554:Benzene / Q000633:toxicity*; D003114:Colony-Forming Units Assay; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D019076:Transgenes; D018631:ras Proteins / Q000235:genetics*
D012333:RNA, Messenger; D018631:ras Proteins; D001554:Benzene