Embryonic toxicokinetic and dynamic differences underlying strain sensitivity to cadmium during neurulation.
Differences in sensitivity are observed between mouse strains, C57 (sensitive) and SWV (resistant) when exposed to cadmium (Cd) during the neurulation period. In this study, we investigated the toxicokinetics of Cd in relation with toxicodynamic responses to identify factors affecting differential Cd-sensitivity in C57 and SWV. Using a level of exposure which induced developmental toxicity and differential effects between strains, we assessed maternal and embryonic Cd uptake and evaluated biomarkers of response previously linked with Cd exposure, specifically metal ion regulators (Mt1, Mt2, DMT1) and markers of cell cycle arrest/apoptosis induction (p53, Cdkn1a, c-Casp3). Greater Cd uptake was observed in C57 embryos compared to SWV and these observations of differential uptake were associated with increased alterations in expression of biomarkers of metal response (e.g. c-Casp3) and strain sensitivity. Using sensitive and resistant mouse strains, we have identified toxicokinetic and dynamic differences which underlie observed differences in Cd embryonic sensitivity and response.
Robinson
Joshua F
JF
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.
Yu
Xiaozhong
X
Hong
Sungwoo
S
Zhou
Chunyan
C
Kim
Nayeon
N
DeMasi
Davide
D
Faustman
Elaine M
EM
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002104:Cadmium / Q000493:pharmacokinetics* / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D054261:Neurulation / Q000187:drug effects*; D013045:Species Specificity; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D015415:Biomarkers; D016159:Tumor Suppressor Protein p53; D002104:Cadmium