PMID- 16369952
OWN - NLM
STAT- MEDLINE
DCOM- 20060327
LR  - 20131121
IS  - 1542-0752 (Print)
IS  - 1542-0752 (Linking)
VI  - 76
IP  - 1
DP  - 2006 Jan
TI  - Interactive effects of cadmium and all-trans-retinoic acid on the induction of 
      forelimb ectrodactyly in C57BL/6 mice.
PG  - 19-28
AB  - BACKGROUND: Most toxicological studies have tested single chemical agents at 
      relatively high doses, and fewer studies have addressed the toxic effects of 
      chemical interactions. It is important to understand the toxicity of chemical 
      mixtures in order to assess the more realistic risks of environmental and 
      occupational exposures. A number of chemicals are known to induce a predominantly 
      postaxial forelimb ectrodactyly in C57BL/6 mice, including acetazolamide, 
      ethanol, cadmium, valproic acid, carbon dioxide, dimethadione, phenytoin, and 
      13-cis-retinoic acid and all-trans-retinoic acid (RA). In the present study, the 
      interactive effects of coadministration of cadmium and RA on developing limbs 
      were investigated. METHODS: Pregnant C57BL/6 mice were treated with different 
      intraperitoneal (IP) doses of cadmium chloride (CdCl2) and/or RA on gestational 
      day (GD) 9.5, and fetuses were collected on GD 18 and double stained for 
      examination of skeletal defects. RESULTS: When RA was given simultaneously with 
      cadmium, a significant increase in the incidence and severity of forelimb 
      ectrodactyly (predominantly postaxial) was observed compared to the results with 
      corresponding doses of cadmium or RA alone. When mice were exposed to 
      subthreshold doses of both cadmium (0.5 mg/kg) and RA (1 mg/kg), the combined 
      treatment exceeded the threshold, resulting in forelimb ectrodactyly in 19% of 
      the fetuses. Moreover, coadministration of cadmium and RA at doses exceeding the 
      respective thresholds showed a synergistic effect, that is, 92% of fetuses were 
      found with the forelimb defect as opposed to 10% if the response were additive. 
      CONCLUSIONS: The findings demonstrate that concurrent exposure to these 
      teratogens can have a synergistic effect and that subteratogenic doses may 
      combine to exceed a threshold.
CI  - Copyright (c) 2005 Wiley-Liss, Inc.
FAU - Lee, Grace S
AU  - Lee GS
AD  - Molecular Toxicology Interdepartmental Program, University of California, Los 
      Angeles School of Public Health, Los Angeles, California 90095, USA.
FAU - Liao, Xiaoyan
AU  - Liao X
FAU - Cantor, Rita M
AU  - Cantor RM
FAU - Collins, Michael D
AU  - Collins MD
LA  - eng
GR  - R01-ES-010413/ES/NIEHS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Birth Defects Res A Clin Mol Teratol
JT  - Birth defects research. Part A, Clinical and molecular teratology
JID - 101155107
RN  - 0 (Teratogens)
RN  - 00BH33GNGH (Cadmium)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Animals
MH  - Cadmium/administration & dosage/*toxicity
MH  - Drug Interactions
MH  - Drug Synergism
MH  - Female
MH  - Forelimb/abnormalities/*drug effects/embryology
MH  - Gestational Age
MH  - Injections, Intraperitoneal
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pregnancy
MH  - Teratogens/*toxicity
MH  - Tretinoin/administration & dosage/*toxicity
EDAT- 2005/12/22 09:00
MHDA- 2006/03/28 09:00
CRDT- 2005/12/22 09:00
PHST- 2005/12/22 09:00 [pubmed]
PHST- 2006/03/28 09:00 [medline]
PHST- 2005/12/22 09:00 [entrez]
AID - 10.1002/bdra.20201 [doi]
PST - ppublish
SO  - Birth Defects Res A Clin Mol Teratol. 2006 Jan;76(1):19-28. doi: 
      10.1002/bdra.20201.