Intraocular neoplasms induced by methylazoxymethanol acetate in Japanese medaka (Oryzias latipes).

Intraocular neoplasms developed in the Japanese medaka, a small fish species, following a single brief exposure to methylazoxymethanol acetate [(MAM-Ac) CAS: 592-62-1]. Specimens 6-10 days old were exposed to doses of MAM-Ac up to 100 mg/liter for 2 hours and then transferred to carcinogen-free water for "grow-out." Of 218 exposed fish examined, 98 (45%) had neoplastic lesions in various stages of development. Of those exposed to 30 mg/liter or more, 57% had the lesions. No lesions were found in eyes or other tissues of 95 control specimens. Early and advanced neoplastic lesions were recognized. Early lesions were characterized by complexes of neoplastic retinal epithelium and tubes that consisted of cells of the sensory retina. Areas of mitotically active, heterogeneous cells associated with such complexes gave rise to advanced neoplasms. We considered the advanced neoplasms to be medulloepitheliomas, which differentiated into three principal cellular patterns: 1) solid masses of unpigmented cells, which frequently showed photoreceptor differentiation as well as ductular formation; 2) heavily pigmented cuboidal to columnar cells resembling retinal epithelium that formed adenomatous patterns; and 3) teratoid medulloepitheliomas. Teratoid medulloepitheliomas, which we considered the most advanced and malignant lesions, consisted of heterogeneous, highly mitotic, invasive cells and contained heteroplastic elements including striated muscle, undifferentiated mesenchymal tissues, and hyaline cartilage. We suggest that MAM-Ac induces hyperplasia of retinal cells followed by establishment of aberrant growth zones containing miscoded cells that give rise to medulloepitheliomas.