Unusual Neoplasms and Hyperplastic Lesions in “Random-bred” Mice Derived from Four-way Crossed Inbred Lines

Tumors, hyperplastic lesions, and heterotopic growths previously considered rare in inbred mice were developed by hybrids derived from C57L/He, 129/Rr, C3HeB/De, and the SWR/Ly inbred strains, and used as test animals in a life-long bioassay for the individual effects of three hormonally active agents: Enovid, Norlestrin, and Clomiphene. No lesions were found associated with drug treatment at the low dose levels used. Types of lesions developed by 150 mice killed at 17.5 or 20.5 months of age include: cystic endometrial hyperplasia, plasma cell leukemia and/or Hodgkins-like reticulum cell sarcoma, adenomatous hyperplasia of the biliary tract mucosa, primary pulmonary tumor, adenomatous hyperplasia of the glandular stomach mucosa and small intestine, Harderian gland tumor, adenomyosis, ovarian tumors of the granulosa cell, stromal cell, and papillary cystadenoma types, adenoma of the anterior pituitary, uterine fibrosarcoma, heterotopia of Brunner's glands, adrenal cortical and medullary tumors, pancreatic islet cell tumors, heterotopic bone and marrow in the spleen, endometrial polyps, and megakaryocytes in the liver or kidney. The types and variety of lesions observed resemble the spectrum seen in man more closely than do those previously observed in any of the inbred parental lines. Their development, coupled with that of glomerulonephritis in some animals, and the absence of amyloidosis, lymphocytic leukemia, and the mammary cancers, among other pathologic states usually developed by the inbred lines, reflect the difficulties of attempting to extend findings from inbred lines to random-mated combinations.