Effects of teratogenic exposures to Zn2+, Cd2+, Ni2+, Co2+, and Cu2+ on metallothionein and metallothionein-mRNA contents of Xenopus embryos.
Xenopus laevis embryos were analyzed for metallothionein by silver-saturation assay and metallothionein-mRNA by reverse transcriptase/polymerase chain reaction following exposures to the following metal chlorides at levels that caused > 95% malformations and < 7% mortality: Zn2+ (300 microM); Cd2+ (18 microM); Ni2+ (56 microM); Co2+ (1,800 microM); and Cu2+ (5.6 microM). At the beginning of the exposure (stages 8), metallothionein-mRNA and metallothionein levels averaged 2.0 x 10(6) copies/embryo and 19 pmol/embryo, respectively. In control embryos at stages 26, 36, 42, and 46, metallothionein-mRNA content averaged 9, 37, 104, and 97 copies x 10(6)/embryo, and metallothionein content averaged 6, 11, 15, and 18 pmol/embryo. In Zn(2+) -exposed embryos at the same stages, metallothionein-mRNA content averaged 116*, 11,400*, 3,210*, and 14 copies x 10(6)/embryo and metallothionein content averaged 10, 18*, 46*, and 90* pmol/embryo; in Cd(2+)-exposed embryos, metallothionein-mRNA content averaged 22, 7,170*, 1,783*, and 240 copies x 10(6)/embryo and metallothionein content averaged 8, 14, 33*, and 56* pmol/embryo, respectively (*P < 0.05 versus controls). Exposure-response curves (Cd2+, 1-18 microM; Zn2+, 3-300 microM) indicated that Cd2+ was 3- to 5-times more potent than Zn2+, based on metallothionein-mRNA response at stage 36 and metallothionein response at stage 46. In Ni(2+)-, Co(2+)-, or Cu(2+)-exposed embryos, metallothionein-mRNA and metallothionein contents did not differ significantly from controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Sunderman
F W
FW
Department of Laboratory Medicine, University of Connecticut Medical School, Farmington 06030-2225, USA.
Plowman
M C
MC
Kroftova
O S
OS
Grbac-Ivankovic
S
S
Foglia
L
L
Crivello
J F
JF
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D001483:Base Sequence; D002104:Cadmium / Q000633:toxicity; D003035:Cobalt / Q000633:toxicity; D003300:Copper / Q000633:toxicity; D004625:Embryo, Nonmammalian / Q000737:chemistry*; D005260:Female; D008297:Male; D008668:Metallothionein / Q000187:drug effects / Q000235:genetics*; D008670:Metals / Q000633:toxicity*; D008969:Molecular Sequence Data; D009532:Nickel / Q000633:toxicity; D012333:RNA, Messenger / Q000032:analysis* / Q000187:drug effects; D013723:Teratogens / Q000633:toxicity*; D014982:Xenopus laevis / Q000196:embryology*; D015032:Zinc / Q000633:toxicity
D008670:Metals; D012333:RNA, Messenger; D013723:Teratogens; D002104:Cadmium; D003035:Cobalt; D003300:Copper; D009532:Nickel; D008668:Metallothionein; D015032:Zinc