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Toxicological Sciences 71, 154-163 (2003)
Copyright © 2003 by the Society of Toxicology

BIOTRANSFORMATION AND TOXICOKINETIC

Cadmium Pathways during Gestation and Lactation in Control versus Metallothoinein 1,2-Knockout Mice

Emmanuel E. Brako*, Allison K. Wilson{dagger}, Margaret M. Jonah{ddagger}, Carmen A. Blum§, Elizabeth A. Cerny§, Kanesha L. Williams§ and Maryka H. Bhattacharyya§,1

* Biology Department, Winona State University, Winona, Minnesota 55987; {dagger} Biological Sciences Department, Benedictine University, Lisle, Illinois 60532; {ddagger} Department of Natural Sciences, Dominican University, River Forest, Illinois 60305; and § Biosciences Division, Argonne National Laboratory, 9700 S. Cass Avenue, Argonne, Illinois 60439

Effects of metallothionein (MT) on cadmium absorption and transfer pathways during gestation and lactation in mice were investigated. Female 129/SvJ metallothionein-knockout (MT1,2KO) and metallothionein-normal (MTN) mice received drinking water containing trace amounts of 109CdCl2 (0.15 ng Cd/ml; 0.074 µCi 109Cd/ml). 109Cd and MT in maternal, fetal, and pup tissues were measured on gestation days 7, 14, and 17 and lactation day 11. In dams, MT influenced both the amount of 109Cd transferred from intestine into body (two- to three-fold higher in MT1,2KO than MTN dams) and tissue-specific 109Cd distribution (higher liver/kidney ratio in MT1,2KO dams). Placental 109Cd concentrations in MT1,2KO dams were three- and seven-fold higher on gestation days 14 and 17, respectively, than in MTN dams. Fetal 109Cd levels were low in both mouse types, but at least 10-fold lower in MTN fetuses. MT had no effect on the amount of 109Cd transferred to pups via milk; furthermore, 85–90% of total pup 109Cd was recovered in gastrointestinal tracts of both types, despite high duodenal MT only in MTN pups. A relatively large percentage of milk-derived intestinal 109Cd was transferred to other pup tissues in both MT1,2KO and MTN pups (14 and 10%, respectively). These results demonstrate that specific sequestration of cadmium by both maternal and neonatal intestinal tract does not require MT. Although MT decreased oral cadmium transfer from intestine to body tissues at low cadmium exposure levels, MT did not play a major role in restricting transfer of cadmium from dam to fetus via placenta and to neonate via milk.

Key Words: metallothionein; cadmium; pregnancy; gestation; lactation; mice.


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