Natural killer cell activity and tumor susceptibility in female mice treated neonatally with diethylstilbestrol.

Female NMRI or AKR/J mice were given daily s.c. injections of 5 micrograms diethylstilbestrol (DES) in 0.025 ml olive oil, or of olive oil only, for the first 5 days after birth. At the age of 6 to 7 weeks, both DES-treated females and control females were killed, and the cytotoxic activity of the spleen cells against standard natural killer cell target YAC-1 cells as well as the natural killer cell-sensitive I-522 cells and relatively insensitive I-51 AKR lymphomas were tested. The cytotoxic activity against I-51 cells was similar for DES-treated and control females while the DES-treated females had only about one-half the cytotoxicity activity to I-522 and YAC-1 cells as did controls. Control females eliminated radioactivity derived from 125I-labeled YAC-1 and I-522 target cells injected i.v. faster than did DES-treated females, while the results were similar for both animal groups when using I-51 cells. The cumulative death incidence was higher for DES-treated females than for control females after incubation with low numbers of I-522 cells but similar for both groups when using I-51 cells. Finally, the incidence of females developing methylcholanthrene-induced sarcomas, using a simple low-dose injection (10 or 20 micrograms), was higher among DES-injected animals than among controls. Taken together, the results indicate that female mice treated neonatally with DES have a functionally defective natural killer cell population, resulting in increased tumor susceptibility.