Abstract

Cadmium is a ubiquitous toxic metal known to cause several adverse health effects in humans. Newborns have an increased gastrointestinal absorption of cadmium compared to adults and seem to be more sensitive to cadmium toxicity. The wellestablished association in adults between increased uptake of dietary cadmium and low iron status has not been investigated in newborns. The aim of this thesis was to study cadmium during the neonatal period, focusing on intracellular transport pathways and interactions of cadmium with calcium and iron. Cadmium-induced effects on the lactating mammary gland were investigated in mice and in murine mammary epithelial HC11 cells. Cadmium reduced total intracellular calcium levels, expression of secretory pathway calcium-ATPase (SPCA) and β-casein gene expression both in vivo and in vitro. An involution-like remodeling of the mammary tissue, including increased fat content, was observed following cadmium exposure. The results indicate that cadmium disturbs the function of the mammary gland by reducing calcium, SPCA and β-casein levels in secreting mammary cells. The impact of iron status on cadmium transport across the neonatal intestine was investigated in suckling piglets and in human immature intestinal epithelial Caco-2 cells. High iron status did not restrict cadmium absorption in the piglets; instead increased cadmium absorption was detected. Similar results were obtained in immature Caco-2 cells. Gene and protein expressions and localizations of the iron transporters DMT1, DMT1-IRE and FPN1 were not affected by iron status, indicating that the mechanism regulating iron absorption is age-dependent. Gene expression of multidrug resistance associated protein 1 (MRP1) was increased in the immature intestinal cells treated with cadmium and correlated to increased transport of cadmium across the cells. In conclusion, cadmium exposure may decrease both calcium and protein levels in milk with potential negative developmental effects in the neonate. Furthermore, iron supplementation does not restrict, but rather increases cadmium absorption in newborns, which should be considered in risk assessment of cadmium.