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.
Papaconstantinou
Andriana D
AD
Center for Devices and Radiological Health, Food and Drug Administration, Rockville, MD 20857, USA.
Brown
Ken M
KM
Noren
Bradley T
BT
McAlister
Terence
T
Fisher
Benjamin R
BR
Goering
Peter L
PL
D000818:Animals; D018053:Arsenites / Q000494:pharmacology*; D002104:Cadmium / Q000378:metabolism / Q000494:pharmacology*; D002642:Chick Embryo; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004622:Embryo, Mammalian / Q000187:drug effects*; D004625:Embryo, Nonmammalian; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D015151:Immunoblotting; D007150:Immunohistochemistry; D008628:Mercury / Q000494:pharmacology*; D014176:Protein Biosynthesis; D013997:Time Factors; D014158:Transcription, Genetic
D018053:Arsenites; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D002104:Cadmium; D003609:Dactinomycin; D008628:Mercury; C015001:arsenite