Hydroquinone, a benzene metabolite, increases the level of aneusomy of chromosomes 7 and 8 in human CD34-positive blood progenitor cells.
Benzene is an established human carcinogen, producing leukemia, hematotoxicity and perhaps lymphoma. Its carcinogenicity is most likely dependent upon its conversion to phenol and hydroquinone, the latter being oxidized to the highly toxic 1,4-benzoquinone in the bone marrow. Exposure of human lymphocytes and cell lines to hydroquinone has previously been shown to cause various forms of genetic damage, including aneusomy and the loss and gain of chromosomes. However, the target cells for leukemogenesis are the pluripotent stem cells or early progenitor cells which carry the CD34 antigen (CD34(+) cells). In this study, human cord blood, which is particularly rich in CD34(+) cells, was exposed to hydroquinone for 72 h in a medium that favored CD34(+) cell survival and growth. CD34(+) and CD34(-) cells were then isolated. Fluorescence in situ hybridization was employed to determine the level of aneusomy of chromosomes 7 and 8 in both cell types. CD34(+) cells were generally more susceptible to aneusomy induction by hydroquinone than CD34(-) cells. Increased trisomy and monosomy of chromosomes 7 and 8 were observed in CD34(+) cells (P(trend) < 0.001), whereas in CD34(-) cells only an increased level of monosomy 7 was detected (P(trend) = 0.002). Particularly striking effects of hydroquinone were observed in CD34(+) cells on monosomy 7 and trisomy 8, two common clonal aberrations found in myeloid leukemias, suggesting that these aneusomies produced by hydroquinone in CD34(+) cells play a role in benzene-induced leukemogenesis.
Division of Environmental Health Sciences, School of Public Health, University of California, 140 Warren Hall, Berkeley, CA 94720-7360, USA. martynts@uclink4.berkeley.edu
M T
MT
Smith
L
L
Zhang
M
M
Jeng
Y
Y
Wang
W
W
Guo
P
P
Duramad
A E
AE
Hubbard
G
G
Hofstadler
N T
NT
Holland
D000782:Aneuploidy; D018952:Antigens, CD34 / Q000097:blood*; D002478:Cells, Cultured; D002897:Chromosomes, Human, Pair 7 / Q000187:drug effects* / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000187:drug effects* / Q000235:genetics; D005312:Fetal Blood / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure*; D006801:Humans; D006873:Hydroquinones / Q000633:toxicity*; D017404:In Situ Hybridization, Fluorescence; D009153:Mutagens / Q000633:toxicity*
D018952:Antigens, CD34; D006873:Hydroquinones; D009153:Mutagens; C031927:hydroquinone