Qualitative and quantitative aspects of human fetal liver metallothioneins

This study examined the status of zinc, copper, and metallothionein (MT) in 31 second trimester (13-23 weeks) human fetal livers. In addition, the metal-binding capacities of concomitant and term placentas were investigated in the light of the role of this organ in transport and binding of the potentially toxic group IIb elements, notably cadmium and mercury. Qualitative analyses indicate that human fetal liver contains three "isoforms" of MT, with the second form (MT-1) being predominant. DEAE A-25 anion exchange chromatography revealed that human fetal hepatic MT-1 and MT-2 elute similarly to native newborn and cadmium-induced adult rat liver MT, MT-1 and MT-2. A significant quantity of a third isoform, which eluted in low-ionic-strength buffer, is also present in human fetal liver. The function of this isoform may be developmental in nature. Quantitative analyses show that MT levels are high (approximately 6.4% of the soluble protein) and correlate well with zinc in human fetal hepatic cytosol. In contrast, copper levels were low, and no significant correlation could be seen with MT. A slight, but significant positive correlation existed between gestational age (in weeks) versus zinc and MT levels (tissue weight basis); after normalizing for protein, no relationship could be observed. Both preterm and term placenta showed low levels of zinc and MT. It is suggested that the low level of cadmium-binding capacity seen in placenta may be one factor in the susceptibility of this organ to cadmium.