Mercury, cadmium, and arsenite enhance heat shock protein synthesis in chick embryos prior to embryotoxicity

BACKGROUND: Cells respond to adverse environmental stimuli by enhancing the expression of specific genes, the products of which include a suite of proteins known as heat shock proteins (hsps), a response often attributed to cellular protection. METHODS:In this study, we characterized alterations in hsp expression in chick embryos (Hamburger‐Hamilton stage 17, 72 h) exposed in ovo to arsenite (As), mercury (Hg), and cadmium (Cd), known developmental toxicants. Embryos were incubated for 2 h following exposure to 3, 10, 30, or 100 nmol metal, or for 2, 4, 12, or 24 h following treatment with 10 nmol metal. RESULTS: An enhanced de novo synthesis of 24‐, 70‐, and 90‐kD, 70‐ and 90‐kD, and 70‐kD proteins was observed with As, Hg, and Cd treatments, respectively. These responses were transient; apparent rates of protein synthesis were maximal 2–4 h after exposure and returned to control rates by 24 h. Actinomycin D experiments demonstrated that arsenite‐induced expression of these proteins is transcriptionally regulated. Immunoblotting experiments identified the 24‐, 70‐, and 90‐kD proteins as the heat shock proteins hsp24, hsp70, and hsp90, respectively. Exposure duration‐related abnormalities were noted in the neural tube with all metals and in the ganglia and somites with Cd and As. Retina, allantois, and limb defects were specific to Cd‐treated embryos, and branchial arch defects were specific to As‐treated embryos. CONCLUSIONS: The data support metal‐induced developmental abnormalities, which are preceded by synthesis of stress proteins. Birth Defects Res B 68:456–464, 2003. Published 2003 Wiley‐Liss, Inc.