High Frequency of Thyroid Tumor Induction by N‐Methyl‐N′‐nitro‐N‐nitrosoguanidine in the Hermaphroditic Fish Rivulus marmoratus

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Abstract
In the self‐fertilizing hermaphroditic fish, Rivulus marmoratus, the susceptibility to tumor induction by N‐methyl‐N‐nitro‐N‐nitrosoguanidine(MNNG) was evaluated. Seven‐day‐old fish larvaewere exposed for 2 h toMNNG at concentrations ranging from 5 to 25 ppm in a static water bath. The exposed fish were observed at 2 and 4 monthsafter carcinogen treatmentto assess tumor development. Within 4‐ months after25 ppmMNNG exposure, nearly all fish developed thyroid tumors. The tumor incidenceswere dose‐ and time‐dependent, and the latent period of tumor induction was less than 2 months. Most induced neoplasms were papillary carcinomas similar histologically to those of rodents and humans, and the tumors were serially transplantable to other fish of the same species. These results demonstratethat rivulus could be useful as a model of thyroid carcinogenesis.