We. Hawkins et al., CARCINOGENIC EFFECTS OF 1,2-DIBROMOETHANE (ETHYLENE DIBROMIDE, EDB) IN JAPANESE MEDAKA (ORYZIAS-LATIPES), Mutation research. Fundamental and molecular mechanisms of mutagenesis, 399(2), 1998, pp. 221-232
The carcinogenicity of 1,2-dibromoethane (ethylene dibromide; EDB) was
investigated in the Japanese medaka (Oryzias latipes), a small fish s
pecies. EDB was administered in water continuously for 97 days to a lo
w concentration group, for 73 days to an intermediate concentration gr
oup, 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 t
ests. 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 i
nside 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 bl
adder papillary adenomas and adenocarcinomas. In separate studies, med
aka exposed to 1.0 lng l(-1) EDB for 2 to 5 weeks had elevated hepatic
glutathione S-transferase activities, possibly indicating induction o
f a pathway that forms the reactive metabolite of EDB in mammals. SDS-
PAGE of hepatic cytosolic fractions of EDB-exposed medaka showed a pro
nounced increase in a band at 26,000 Da, the expected position for GSH
-S-transferase, Although little is known about EDB's mechanisms of act
ion, medaka appear exceptionally sensitive to the carcinogenic effects
of EDB and could serve as a model test species for studying similar c
ompounds. (C) 1998 Elsevier Science B.V. All rights reserved.