Modulation of lymphokine-activated killer cell-mediated cytotoxicity by estradiol and tamoxifen.
The effect of tamoxifen (TX) and estradiol (E2) on interleukin-2 (IL-2 )-activated killer (LAK) cell-mediated cytotoxicity was examined using spleen cells of Fischer 344 rats as the source of effectors and P815 murine mastocytoma cells as targets. Treatment of target cells with either TX or E2 for 4 or 18 hr rendered them highly sensitive to LAK cell-mediated lysis. When TX and E2 were applied jointly, cytotoxicity remained at the level of TX alone. The cytotoxic potential of IL-2-primed LAK cells was not modified consistently by TX and E2. When TX-treated target and effector cells were combined, high cytotoxicity characteristic of sensitized target cells was observed. In similar experiments with E2-treated cells, both enhancement and inhibition of cytotoxicity by treated effector cells was seen in some designs. Target cells could be sensitized for LAK cell-mediated destruction by physiological concentrations (1 nM) of E2 and equimolar concentration of TX. Sensitization led to the accelerated release of the nuclear label 3H-thymidine from target cells after cytotoxic insult and could be prevented by treatment with the metabolic inhibitors cycloheximide and actinomycin D. Enhanced 3H-thymidine release from TX-treated targets was also demonstrated after induction of Ca2+ influx by exposure to the ionophore A23187. Neither E2 nor TX exerted a direct cytotoxic effect on P815 cells. P815 cells had no classical receptors for E2 or progesterone.
Baral
E
E
Manitoba Cancer Treatment and Research Foundation, Winnipeg, Manitoba, Canada.
Nagy
E
E
Berczi
I
I
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D011916:Rats, Inbred F344; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004965:Estrogen Antagonists; D013629:Tamoxifen; D004958:Estradiol