Differential expression of cytochrome P450 genes associated with benzene-induced hematotoxicity.
Zhao-ZW; Bi-YY; Xia-Y; Tao-N; Ma-Q
FASEB J 2007 Apr; 21(6)(Suppl):A1181
Benzene is an established human carcinogen and leukemogen. Chronic benzene exposure results in progressive depression of bone marrow function with increased risks of aplastic anemia, myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), chronic lymphocytic leukemia, and other disorders. The mechanism underlying benzene toxicity remains uncertain; an initial metabolism and bioactivation of benzene, especially by CYP2E1 in the liver, was considered a prerequisite. To identify CYP genes whose expression is aberrant in benzene poisoning, a cDNA microarray containing 32 CYP genes was used to detect differential expression of CYPs in patients with hematopoietic dysfunction of benzene exposure. Seven female shoemakers with hematological disorders (six cases of decreased peripheral white blood cells and one case of aplastic anemia) were recruited, and seven age- and gender-matched normal subjects were selected as controls. Total RNA from the two groups was prepared, followed by reverse transcription to cDNAs with concomitant incorporation of fluorescent dCTP (Cy3 for the patients and Cy5 for the controls). Microassay was performed. Genes with a two-fold higher/lower expression level were considered to be significant. Six CYP genes (CYP4F3, CYP1A1, CYP27A1, CYP1B1, CYP2B6, and CYP51) were found to be differentially expressed between benzene-exposed patients and controls. Among these, CYP4F3 gene was up-regulated consistently among all patients. Our study indicated that CYP4F3 is up-regulated in peripheral blood cells in bezene poisoning and may serve as a new biomarker for the exposure and poisoning of benzene.
Cellular-function; Cellular-structures; Cell-differentiation; Cell-function; Cell-biology; Humans; Cancer; Chemical-analysis; Biochemical-analysis; Leukocytes; Blood-disorders; Blood-analysis; Hemolytic-anemia; Hematology; Hemodynamics; Poison-control; Bone-disorders; Age-factors; Genetic-factors
Health Effects Laboratory Division, CDC National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV, 26505
Abstract; Conference/Symposia Proceedings
The FASEB Journal