Large granular lymphocyte (LGL) leukemia commonly occurs in the Fischer-344/N rat. The high spontaneous incidence complicates the interpretation of results from chronic carcinogenicity studies that use this rat strain. As a result, a comprehensive characterization of LGL leukemia is necessary to help understand the leukemogenic process and the applicability of staging for assessing the progression of this disease. In the current study, the proliferation rate of LGL leukemia cells from untreated control Fischer-344 (F-344) rats in 3 stages of leukemia compared to nonleukemic age-matched rats was determined by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). In histologic sections of spleen from aged F-344/N rats affected by LGL leukemia, there was a significant increase of both PCNA labeling and mitotic indices that was most advanced in the spleen of rats with more severe LGL leukemia. These results support biological significance for the morphologic staging system currently in use.
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