Dose-Response Studies to Polyoma Virus in Rats 2

Newborn, inbred, polyoma-free Wistar/Furth (W/Fu) rats were inoculated intravenously with 0.05 ml of increasing dilutions (10−0.3–10−4) from a common pool of polyoma virus. The response of W/Fu rats to polyoma virus was measured with respect to three parameters: tumor frequency, survival times, and histologic types of polyoma tumors. As expected, tumor frequency was markedly increased and survival times were markedly decreased with increasing virus dose. The histologic types of polyoma tumors also varied with virus concentration. The inoculation of the highest virus doses (100 and 10−0.3) resulted in the formation of multiple capillary, cystic, or cavernous hemangiomas in the brain or spinal cord. Massive hemorrhages from these hemangiomas caused death within 14 to 29 days after birth. Medium virus doses (10−1–10−2.3 dilutions) induced multiple tumors including renal sarcomas, hemangiomas, mesenchymomas, osteogenic sarcomas, exostoses of bones, and an occasional subcutaneous fibromatosis. The mean survival times for rats receiving intermediate doses ranged from 28 to 42 days post partum. Low virus doses (10−3–10−3.3 dilutions) caused a single tumor, usually a renal sarcoma, after long survival times (63–110 days). Hemangiomas did not occur in the low virus-dose groups. The three dose-dependent response patterns were referred to as “hemangiomatous response,” “multiple tumor response,” and “late tumor response.” To detect strain differences in the tumor frequency from polyoma virus, the standard polyoma virus pool was inoculated intravenously in dilutions 100 or 10−2 into newborn Wistar, noninbred Sprague-Dawley, and inbred August rats. No strain differences were found with the undiluted virus pool. Tumor frequency after injection of a 10−2 dilution was 84 to 86 percent for the two noninbred strains as opposed to 35 percent for the inbred strain. Susceptibility of rats to oncogenesis by polyoma virus ceased after the 7th day post partum.