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Occurrence of Thymic Lymphoma in Carcinogenesis Bioassay Specimens of the Japanese Medaka (Oryzias latipes)¹

Gulf Coast Research Laboratory, Ocean Springs, Mississippi 39564

Multiple cases of thymic lymphoma were diagnosed in bioassay specimens of Japanese medaka (Oryzias latipes), a small fish species. Lymphoma in chemically exposed specimens was not clearly related to specific compounds, dose, or sex. Multiple cases of lymphoma occurred in three specimens held in one aquarium and in two specimens in two other aquaria, suggesting the possibility of horizontal transmission. Forty cases were observed in 9802 specimens (0.41%), with an incidence of 0.46% in exposed specimens (5690 total) and 0.34% in controls (4112 total). Lesiosn were dominated by small cells with large, basophilic nuclei and a thin cytoplasmic rim. Mitotic figures were frequently observed. Electron microscopy showed that the nuclei of lymphoma cells were highly invaginated but revealed no viral particles. Lymphomas appeared to originate in the thymus and subsequently infiltrate esophagopharyngeal regions, retroperitoneal spaces, cranial regions, heart, and abdominal viscera. Given the scattered occurrence of the lymphomas and the fact that they tend to occur in specimens in contact with one another, we suspect a viral etiology. Lymphoma appears to be the most frequently occurring spontaneous neoplasm in medaka and should be taken into account when assessing results of carcinogenesis studies.