Carcinogenic effects of 1,2-dibromoethane (ethylene dibromide; EDB) in Japanese medaka (Oryzias latipes)

Abstract

The carcinogenicity of 1,2-dibromoethane (ethylene dibromide; EDB) was investigated in the Japanese medaka (Oryzias latipes), a small fish species. EDB was administered in water continuously for 97 days to a low concentration group, for 73 days to an intermediate concentration group, and intermittently for 24 h once each week over 97 days to a high concentration group. Medaka were 7 days old at the beginning of the tests. Mean measured EDB concentrations in the ambient water were 0.13 mg l-1, 6.20 mg l-1, and 18.58 mg l-1 in the low, intermediate, and high concentration groups, respectively. Two control groups, one inside and one outside the exposure apparatus, were used. Samples were examined histologically at 24, 36, and 58 weeks from the beginning of the tests. EDB was clearly carcinogenic to medaka in the intermediate and high concentration groups causing (1) hepatocellular adenomas and carcinomas, (2) cholangiomas, (3) chloangiocarcinomas, and (4) gall bladder papillary adenomas and adenocarcinomas. In separate studies, medaka exposed to 1.0 mg l-1 EDB for 2 to 5 weeks had elevated hepatic glutathione S-transferase activities, possibly indicating induction of a pathway that forms the reactive metabolite of EDB in mammals. SDS-PAGE of hepatic cytosolic fractions of EDB-exposed medaka showed a pronounced increase in a band at 26,000 Da, the expected position for GSH-S-transferase. Although little is known about EDB's mechanisms of action, medaka appear exceptionally sensitive to the carcinogenic effects of EDB and could serve as a model test species for studying similar compounds.