Jg. Cory et al., DEOXYADENOSINE-RESISTANT MOUSE LEUKEMIA-L1210 CELL-LINES WITH ALTERATIONS IN EARLY RESPONSE GENES AND P53, Anticancer research, 16(6B), 1996, pp. 3483-3489
L1210 cell lines selected for resistance to deoxyadenosine exhibit alt
ered steady-state levels of the mRNA for the early response genes and
p53. In the deoxyadenosine-resistant cell lines (Y8 and ED2), the leve
ls of the mRNAs for p53 and c-jun were markedly decreased while the st
eady-state levels for mRNAs for c-myc, c-fos and jun B were elevated i
n the Y-8 and ED2 cell lines. The levels of the mRNAs for PCNA and c-m
yb were the same in the wild type and mutant cell lines. The levels of
the mRNAs for krox-24 were extremely low in the wild type and mutant
cell lines. Cycloheximide (CHX) treatment of the cells resulted in the
increase in the mRNA levels for c-jun, jun B, krox 24 and p53 in the
Y-8 and ED2 cell lines. The time courses and the extents of the increa
ses in the mRNA levels following CHX treatment were not the same for a
ll of these mRNAs. The level of p53 RNA increased with no lag followin
g CHX treatment while the levels of the mRNAs for c-myc, c-jun and kro
x-24 increased after a one-hour lag period. The level of the mRNA for
p53 and c-myc increased 20- and 7- fold respectively while the mRNA le
vel for knox-24 increased 80-fold following CHX treatment The Y8 and E
D2 cell lines that lack steady-state levels of p53 show decreased sens
itivity to cisplatin and increased frequency of gene amplification as
measured by PALA resistance in a manner similar to other cell lines la
cking p53. On the other hand, the ED2 and Y8 cell lines do not show a
GI-block in response to PALA treatment. The cell lines appear to offer
an experimental system in which to study the interactions between/amo
ng these ear;ly response genes and the p53-dependent and independent p
athways.