Use of the Japanese Medaka (Oryzias latipes) and Guppy (Poecilia reticulata) in Carcinogenesis Testing Under National Toxicology Program Protocols

Abstract

A need exists for whole animal toxicity, mutagenesis, and carcinogenesis models that are alternative to the traditional rodent test models and that are economical, sensitive, and scientifically acceptable. Among small fish models, the Japanese medaka (Oryzias latipes) is preeminent for investigating effects of carcinogenic and/or toxic waterborne hazards to humans. The guppy (Poecilia reticulata), although less widely used, is valuable as a comparison species. Both species are easy to maintain and handle in the laboratory and there is a large body of background information on their responsiveness to a range of classes of carcinogens. There are considerable data on the occurrence of background diseases and on spontaneous neoplastic lesions, both of which occur relatively rarely. With few modifications, the medaka and guppy are amenable to carcinogenicity testing under the rigid standards established by the National Toxicology Program (NTP) for rodent tests. The advantages of the small fish in carcinogenesis studies are best realized in long-term studies that involve environmentally realistic exposures. Studies to identify chronic effects can be conducted in about 12 months, near the life span of medaka in our laboratory. Practically, 9-month studies are optimal but shorter study cycles and a variety of exposure/growout and initiation/promotion scenarios are available. Studies on 3 compounds tested in medaka under NTP protocols are under review and preliminary analysis indicates that chronic carcinogenicity bioassays with medaka, guppy, and potentially with other small fish species are feasible and scientifically valid.

Silver nanospheres are cytotoxic and genotoxic to fish cells

“…The explanation for this difference is uncertain and may reflect either a different genotoxic potential for silver versus titanium nanoparticles or it may simply reflect the greater sensitivity of the chromosomal aberration assay compared to the micronucleus assay. It should be noted that medaka fish have been used extensively as a model for human health (Hawkins et al, 2003; Shima and Mitani, 2004; Kasahara et al, 2007). Thus, these data have implications for the potential effects of silver nanoparticles on aquatic species, and they also imply that there could be a concern for humans as well.…”

“…Because of the potential for environmental exposures from these sources, we have initially focused on cultured cells from medaka, a small, teleost fish that is a well-established model aquatic organism (Hawkins et al, 2003; Shima and Mitani, 2004; Kasahara et al, 2007). Silver nanoparticles have been shown to be toxic to fish inducing death, changes in gene expression and embryotoxicity (Asharani et al, 2008; Griffitt et al, 2008, 2009).…”

Generation of medaka gene knockout models by target-selected mutagenesis

“…Furthermore, fish models are being embraced because of their extended similarity in mutagenesis and carcinogenesis processes with rodent models and possibly humans [2]. The development of fish mutants will provide additional tools to explore the mechanisms of these processes.…”

Medaka (Oryzias latipes) as a sentinel species for aquatic animals: Medaka cells exhibit a similar genotoxic response as North Atlantic right whale cells

“…Medaka is a small, teleost fish that is a well-established research model organism for carcinogenesis testing (Hawkins et al, 2003). Although medaka is primarily a freshwater fish, they tolerate a wide range of salinity and have been used as a marine model as well (Tachikawa et al,1991; McElroy et al, 2006).…”