Hormesis: A stress response in cells exposed to low levels of heavy metals

Abstract

Cytotoxicity studies using a 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MT)-based in vitro toxicity assay revealed that McCoy cells exposed to low concentrations of mercuric (0.7 yM),cadmium (1 1M) and cupric chloride (3 tIM) exhibited significant increases in cellular activity. This increased activity, previously termed hormesis, coincided with the production ofhigh levels ofthe stress proteins, heat shock protein 70 (Hsp 70) and metallothionein, while the high constitutive expression of these proteins in cadmium-resistant mutant (CRM) cells corresponded to constitutive hormetic activity. Hormesis was found to obey uniform kinetics allowing for a mathematical description of this increased activity. These results suggest that hormetic activity is a specific cellular response, and most likely, a stress response to low but harmful levels of toxic agents and may therefore provide a rapid test for the presence of toxicants at concentrations associated with chronic toxicity.