Bcl-2 and its homologue Bcl-XL are expressed in a variety of tumors an
d their expression modulates the sensitivity of tumor cells to a wide
spectrum of chemotherapeutic agents and gamma-irradiation. In the pres
ent report, we generated clones of FL5.12 lymphoid cells with similar
levels of Bcl-2 and Bcl-XL using the Flag epitope to determine if thes
e survival proteins could provide equivalent protection when challenge
d with chemotherapy or gamma-irradiation. Using four M-phase specific
chemotherapeutic agents, Bcl-XL and Bcl-2 provided similar protection
against vincristine and vinblastine whereas Bcl-XL afforded as much as
50% greater cell viability than Bcl-2 against etoposide and teniposid
e-induced cell death. In addition, Bcl-XL provided significantly great
er cell viability than Bcl-2 against methotrexate, fluorouracil, and h
ydroxyurea, three S-phase specific agents. In apoptosis induced by gam
ma-irradiation and cisplatin, two antitumor treatments that are cell-c
ycle phase-nonspecific agents, both Bcl-XL and Bcl-2 conferred similar
protection against gamma-irradiation, but Bcl-XL provided better prot
ection than Bcl-2 against cisplatin. These results indicate that Bcl-X
L and Bcl-2 confer a differential ability to protect against chemother
apy-induced cell death, which appears to be dependent on the molecular
mechanism targeted by the drug rather than its cell-cycle phase speci
ficity. (C) 1997 by The American Society of Hematology.