Q. Li et al., DIFFERENTIAL INHIBITION OF DNA-SYNTHESIS IN HUMAN T-CELLS BY THE CIGARETTE TAR COMPONENTS HYDROQUINONE AND CATECHOL, Fundamental and applied toxicology, 38(2), 1997, pp. 158-165
Hydroquinone (HQ), catechol, and phenol exist in microgram quantities
in cigarette tar and represent the predominant form of human exposure
to benzene. Exposure of human T lymphoblasts (HTL) in vitro to 50 mu M
HQ or 50 mu M catechol decreased IL-2-dependent DNA synthesis and cel
l proliferation by > 90% with no effect on cell viability. phenol had
no effect on HTL proliferation at concentrations up to 1 mM. The addit
ion of HQ or catechol to proliferating HTL blocked H-3-TdR uptake by >
90% within 2 hr without significantly affecting H-3-UR uptake, sugges
ting that both compounds inhibit a rate-limiting step in DNA synthesis
. However, the effects of HQ and catechol appear to involve different
mechanisms. Ferric chloride (FeCl3) reversed the inhibitory effect of
catechol, but not HQ, corresponding with the known ability of catechol
to chelate iron. HQ, but not catechol, caused a decrease in transferr
in receptor (TfR, CD71) expression, comparable to the level observed i
n IL-2-starved cells. HQ also inhibited DNA synthesis in cultures of t
ransformed Jurkat T lymphocytes, primary and transformed fibroblasts,
and mink lung epithelial cells, indicating that its antiproliferative
effect was not restricted to IL-2 mediated proliferation. However, DNA
synthesis by primary lymphocytes was more sensitive to HQ (IC50 = 6 m
u M) than that of the transformed Jurkat T cell line (IC50 = 37 mu M)
or primary human fibroblasts (IC50 = 45 mu M), suggesting that normal
lymphocytes may be particularly sensitive to HQ. The effects of HQ and
catechol on DNA synthesis could be partially reversed by a combinatio
n of adenosine deoxyribose and guanosine deoxyribose, suggesting that
both compounds may inhibit ribonucleotide reductase. (C) 1997 Society
of Toxicology.