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Toxicological Sciences 60, 184-192 (2001)
Copyright © 2001 by the Society of Toxicology

SYSTEMS TOXICOLOGY

Increased Metallothionein in Mouse Liver, Kidneys, and Duodenum during Lactation

Daniel Solaiman*,{dagger}, Margaret M. Jonah{dagger},{ddagger}, Wesley Miyazaki{dagger}, Gloria Ho{dagger} and Maryka H. Bhattacharyya{dagger},1

* Department of Chemistry, Eastern Regional Research Center, ARS U.S. Department of Agriculture, 600 East Mermaid Lane, Philadelphia, Pennsylvania 19118; {dagger} Biosciences Division, Argonne National Laboratory, Argonne, Illinois 60439; and {ddagger} Department of Natural Sciences, Dominican University, 7900 West Division Street, River Forest, Illinois 60305

Lactation-induced increases in cadmium absorption and retention have been demonstrated in mid-lactating mice, but no systematic measurements of endogenous metal-binding protein concentrations during lactation have been reported. Using Cd/hemoglobin radioassay, this study detected significant increases in metallothionein (MT) concentrations in liver (4-fold), kidneys (2-fold), and duodenum (2-fold), but not jejunum, of mouse dams on days 13 and 20 of lactation. These increases occurred in the absence of cadmium exposure and were specific to the lactation period; dams 5 days after weaning showed MT levels that were similar to those of nonpregnant (NP) mice. Similarly, Northern blot analyses of livers from lactating mice demonstrated that MT mRNA concentrations in maternal liver during mid-lactation were 6-fold higher than those observed 5 days after pups were weaned. Gel filtration of final supernatants from the Cd/hemoglobin assay confirmed that the Cd-binding molecule induced during lactation was indeed metallothionein. In addition, chromatographic analyses of cytosols from tissues taken from dams administered small amounts of Cd (66 ng/mouse) showed that the trace amounts of Cd absorbed through the maternal gastrointestinal tract during mid-lactation were also bound to the MT. These results indicate MT induction in mouse dams occurs as a physiological consequence of lactation, requiring no external stimulus. This induced MT participates in binding low levels of dietary cadmium consumed by the dam. During lactation, elevated maternal MT may affect pathways for essential trace metals as well as sequester toxic metals harmful to the neonate. Multiparous humans may have increased risk of accumulating environmental Cd.

Key Words: metallothionein; cadmium exposure; environmental cadmium; lactation; liver; kidneys; duodenum; mouse.


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E. E. Brako, A. K. Wilson, M. M. Jonah, C. A. Blum, E. A. Cerny, K. L. Williams, and M. H. Bhattacharyya
Cadmium Pathways during Gestation and Lactation in Control versus Metallothoinein 1,2-Knockout Mice
Toxicol. Sci., February 1, 2003; 71(2): 154 - 163.
[Abstract] [Full Text] [PDF]


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