Combined effects of interferon and steroid hormones on 2',5'-oligoadenylate synthetase activity in chronic lymphocytic leukemia cells.
2',5'-oligoadenylate synthetase (OAS) has been implicated in the effects of interferons (INF) and steroid hormones on cell growth and differentiation. We studied the combined effects in vitro of hormones and INF on OAS activity in cells from 10 patients with chronic lymphocytic leukemia. IFN enhanced OAS activity in all cells studied and also induced morphologic transformation. Diethylstilbestrol was also found to induce OAS activity, but not morphologic transformation. Progesterone, tamoxifen and dihydrotestosterone had no effect on enzyme activity nor on morphology. In five samples, all with estrogen receptor activity, DES and INF were synergistic in inducing OAS activity. TAM-INF synergism was observed in one sample. DES and TAM did not, however, significantly enhance IFN-induced morphologic transformations. Hydrocortisone reduced OAS activity, and antagonized INF-induced enzyme activity and morphologic transformations. We conclude that hormones can modulate OAS activity in CLL cells. These findings may be of importance in the design of INF-based therapies of CLL.
Triozzi
P L
PL
Department of Medicine (Hematology/Oncology), Ohio State University, Columbus 43210.
Avery
K B
KB
Abou-Issa
H M
HM
Chou
T C
TC
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D015448:Leukemia, B-Cell / Q000201:enzymology*; D008297:Male; D011987:Receptors, Steroid / Q000502:physiology; D011994:Recombinant Proteins; D013256:Steroids / Q000494:pharmacology*
D007370:Interferon Type I; D011987:Receptors, Steroid; D011994:Recombinant Proteins; D013256:Steroids; D007371:Interferon-gamma; D015088:2',5'-Oligoadenylate Synthetase