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SM Hsu, X Zhao, S Chakraborty, YF Liu, J Whang-Peng, MS Lok and S Fukuhara
Department of Pathology, University of Texas Health Science Center, Houston
77225.
We compared the proliferation of mononuclear and multinuclear cells in four
Hodgkin's cell lines, HDLM-1, HDLM-1d, L-428, and KM-H2, by examining their
capacity to incorporate bromodeoxyuridine (BrdUrd) into nuclei.
Approximately 5% of all cells in HDLM-1 cultures had two or more nuclei, a
characteristic of Reed-Sternberg (RS) cells. Unlike mononuclear Hodgkin's
(H) cells, these RS cells exhibited no uptake, or only minimal uptake of
BrdUrd, suggesting that they did not replicate actively. Cytogenetic study
showed that 25% of the HDLM-1 cells contained a tetraploid (4X) set of
chromosomes with a characteristic two-peak distribution. Following
treatment of HDLM-1 cells with phorbol ester, the percentages of 4X cells
and RS cells increased to 50% and 12%, respectively. This increase in RS
cells was not likely to be due to cell fusion as shown by the absence of
hybridization of BrdUrd- positive and -negative nuclei. Phorbol ester has a
short-term effect of blocking the exit of cells from G1 into S phase, but
no effect on the transition from S phase to G2/M phase. The block is more
prominent in 2X cells than in 4X cells, which may explain the increase in
percentage of 4X cells in phorbol ester-treated cultures. In addition,
phorbol ester induced the differentiation of H-RS cells, which was
accompanied by loss of the marker HeFi-1 from the cell surface.
Approximately one third of the RS cells did not express HeFi-1, or
expressed only minimal amounts. The findings led us to the following
conclusions: (1) The 4X cells probably are formed from 2X H cells as a
result of disturbed cytokinesis, but not a cell fusion. (2) A considerable
number of 4X cells were H cells, because the number of 4X cells
consistently exceeded that of RS cells. (3) Since mitotic figures are
extremely rare in RS cells and these cells did not show active BrdUrd
uptake, the increased number of RS cells must also be a consequence of
disturbed cytokinesis of H cells or a result of nuclear transformation
(twisting, convolution, or separation of the nucleus) in H cells. (4) Most
RS cells lose their proliferating capacity and some RS cells may undergo
further differentiation. Uptake of BrdUrd and phorbol ester induction were
also studied on the other three H-RS cell lines, HDLM-1d, L-428, and KM-H2,
with results similar to those for HDLM-1.
This article has been cited by other articles:
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| Copyright © 1988 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||