DEOXYADENOSINE-RESISTANT MOUSE LEUKEMIA-L1210 CELL-LINES WITH ALTERATIONS IN EARLY RESPONSE GENES AND P53

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.