Hg- and Cu-induced hepatocellular changes in the mummichog, Fundulus heteroclitus.
To investigate mechanisms by which the mummichog (F. heteroclitus) successfully withstands heavy metal pollution, fish were treated with Hg2+ at up to 0.10 mg/L, Cu2+ at up to 1.0 mg/L, or combinations of Hg2+ and Cu2+. In earlier work, protein analysis of liver indicated that most of the cytosolic Cu is bound to the sulfhydryl-rich metallothionein, but that Hg is not associated with cytosolic proteins. Morphometric analysis indicates the Hg-treatment increases the lipid compartment of hepatocytes (ANOVA, F = 10.73, p less than 0.01). This lipid increase is correlated with the Hg content (analyzed by atomic absorption spectrophotometry) of individual liver samples (Spearman rank correlation, rs = 0.621, p less than 0.01). Cu treatment causes a reduction in the lipid compartment (F = 10.38, p less than 0.01), reduced cytoplasm in general (F = 18.55, p less than 0.001) and an increased lysosome count (F = 14.21, p less than 0.001). X-Ray microanalysis locates Cu in secondary lysosomes, but not in other organelles. Results of treatment with both Hg2+ and Cu2+ are similar to those of Hg2+ alone. Concentrations of Cu in liver varied too much to allow assessment of correlations with cytoplasmic changes. Usual mechanisms for handling toxic heavy metals include binding to metallothionein and sequestering in lysosomes. Our findings for Cu are in agreement with this. Fish, however, can methylate Hg. (We have found greater than 75% of killifish hepatic Hg to be methylated.) Increased cellular lipid may be a mechanism for sequestering the lipid-soluble methylmercury.
P
P
Weis
J D
JD
Bogden
E C
EC
Enslee
D000818:Animals; D002451:Cell Compartmentation; D003300:Copper / Q000378:metabolism / Q000494:pharmacology*; D005399:Fishes / Q000378:metabolism*; D007695:Killifishes / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008247:Lysosomes / Q000648:ultrastructure; D008628:Mercury / Q000378:metabolism / Q000494:pharmacology*; D008854:Microscopy, Electron
D003300:Copper; D008628:Mercury