Cadmium accumulation and distribution in human lung fibroblasts

Abstract

An investigation was conducted on cadmium accumulation and its molecular distribution in growing cultures of human fetal lung fibroblasts (IMR-90). For the first 24–48 h post-exposure, the amount of cadmium per cell remained low and relatively constant; more than 50% of the intracellular Cd was associated with molecular weight components less than 2000 daltons. The presence of a Cd-binding component with a molecular weight of 11 800 daltons was also detected during this initial period. Based upon its molecular size, sensitivity to trypsin, and ability to coincorporate 35S along with 115Cd, we have concluded that this component is a protein. Its similarity to metallothionein was suggested by its molecular size, low level in cells never exposed to Cd, spectral properties, and heat stability. During the late log phase of growth, accumulation of Cd by fibroblasts occurred at a near-linear rate and the intracellular Cd level was proportional to the exogenous concentration. There was a corresponding increase in the amount of the fibroblast Cd-binding protein present, accompanied by a reduction in the amount of Cd associated with low molecular weight components. Synthesis of the Cd-binding protein appeared to occur at a more rapid rate than accumulation suggesting that its presence may be necessary for Cd transport and/or accumulation, an interpretation strengthened by the finding that cells previously passaged in Cd exhibited no lag in accumulation and accumulated 8–10-fold more Cd. By 168 h post-exposure, a plateau occurred in the intracellular Cd level as well as the amount of Cd-binding protein present. After this period, a redistribution of Cd from the metallothionein-like protein to high molecular weight proteins occurred. It is possible that this redistribution might be the cellular event that triggers the pathological changes known to occur after Cd-grown cultures have reached confluency.