INTERLEUKIN 12-MEDIATED PREVENTION OF SPONTANEOUS MAMMARY ADENOCARCINOMAS IN 2 LINES OF HER-2 NEU TRANSGENIC MICE/

The ability of interleukin, (IL)-12 to prevent tumors when administere d to individuals with a genetic risk of cancer was studied in two line s of transgenic mice expressing rat HER-2/neu oncogene in the mammary gland. Female BALB/c (H-2(d)) mice carrying the activated HER-2/neu on cogene show no morphological abnormalities of the mammary gland until 3 wk of age. They then progress through atypical hyperplasia to in sit u lobular carcinoma and at 33 wk Of age all 10 mammary glands display invasive carcinomas. Adult FVB mice (H-2(q)) carrying the HER-2/neu pr otooncogene develop mammary carcinomas with a longer latency (38-49 wk ) and a lower multiplicity (mean of 2.6 tumors/mice). Treatment with I L-12 (5 daily intraperitoneal injections, 1 wk on, 3 wk off; the first course with 50 ng IL-12/day, the second with 100 ng IL-12/day) begun at 2 wk of age in BALB/c mice and at 21 wk of age in FVB mice markedly delayed tumor onset and reduced tumor multiplicity. Analogous results were obtained in immunocompetent and permanently CD8+ T lymphocyte-de pleted mice. In both transgenic lines, turner inhibition was associate d with mammary infiltration of reactive cells, production of cytokines and inducible nitric oxide synthase, and reduction in microvessel num ber, in combination with a high degree of hemorrhagic necrosis.