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Stage-dependent Induction of Prenatal Tumors in Mice by the Kirsten and Moloney Strains of Murine Sarcoma Viruses¹

Laboratory of in Vivo Carcinogenesis, Institute of Clinical and Experimental Oncology, School of Medicine, University of Genoa, and Istituto Nazionale per la Ricerca sul Cancro di Genoa [L. R., O. B., S. A., D. U.], and Institute of Microbiology, School of Medicine, University of Genoa [O. E. V.], Viale Benedetto XV, 10, 16132 Genoa, Italy

The Moloney (MoMSV) and Kirsten (KiMSV) strains of murine sarcoma viruses are known to induce mesenchymal sarcomas upon infection of newborn rodents. To determine their activity in mouse embryos, 11- to 15-day-pregnant CD-1 mice were laparotomized, and the single implants were inoculated into the abdominal portion of the embryonal body with an average of 15 and 1500 focus-forming particles/g of body weight of the MoMSV and KiMSV viruses, respectively. Another group of less than 1-day-old pups was given a comparable amount of either virus. Tumors appeared in the young within the first few weeks of life with incidences and histological types dependent on the gestational day and the viral strain inoculated. Mixed mesenchymal sarcomas at or near the site of inoculation and vascular tumors of the brain were by far the most frequent neoplasms observed in the newborn. With MoMSV there was an increased incidence of sarcomas with advancing age at treatment, being 0% at 11 days of pregnancy and 96% in newborn (P for trend, <0.025). By contrast, KiMSV caused an incidence of sarcomas below 20% throughout (P for trend, >0.05).

Brain tumors were identified in the several MoMSV and KiMSV groups, with a peak value of 43% following the inoculation of both viruses into 13- and 15-day-old embryos, respectively. While the total incidence of these tumors was significantly different from controls, no positive trend by day of treatment was found among the MoMSV and KiMSV viruses (P < 0.05). The tumors were mainly capillary angiomas, but a few cavernous angiomas were also detected. In addition, eight pups which were given injections of both viruses at developmental Days 11 to 13 had tumors of the choroid plexus. In many instances, newborn pups were affected by multiple vascular abnormalities of the brain, including capillary telangiectases and multiple hemorrhagic areas. No such lesions nor tumors at any site were found among the control animals.

The present results are important not only because of the evidence that Swiss embryos respond selectively to the carcinogenic effects by murine sarcoma viruses, but also because they offer the opportunity to dissect directly in vivo the mechanisms underlying the stage-related sensitivity of prenatal mice to oncogenic retroviruses.

¹ This work was supported by Consiglio Nazionale delle Ricerche, Roma, Italy (Progetto Finalizzato Oncologia, Contracts 84.00776.44 and 84.00838). Additional support was provided by AIRC Grant 84.01841.

² To whom requests for reprints should be addressed.

Received 4/15/85. Revised 8/12/85. Accepted 8/14/85.