PMID- 8248859
OWN - NLM
STAT- MEDLINE
DCOM- 19931229
LR  - 20141120
IS  - 0040-3709 (Print)
IS  - 0040-3709 (Linking)
VI  - 48
IP  - 3
DP  - 1993 Sep
TI  - Chloroquine embryotoxicity in the postimplantation rat conceptus in vitro.
PG  - 213-26
AB  - The embryotoxicity of the antimalarial drug chloroquine (CQ) was evaluated in 
      vitro using the rat whole embryo culture system. CQ was found to be embryotoxic 
      and dysmorphogenic when added directly to the culture media containing 
      gestational day (GD) 10 rat conceptuses. Twenty-six-hr exposure to CQ elicited 
      dose-related decreases in embryonic crown-rump length, protein and DNA contents 
      and increases in the incidence of morphologically abnormal embryos. At 30 microM 
      CQ, embryonic protein content was decreased to 67% and DNA content to 58% of 
      control while the incidence of morphological abnormalities rose to 100%. Abnormal 
      axial rotation, micro-ophthalmia, and selective cephalic hypoplasia were the most 
      common developmental abnormalities observed. Visceral yolk sac (VYS) vasculature 
      and blood pigmentation were also decreased in a dose-dependent manner, as was VYS 
      DNA content (80% of control at 30 microM). VYS protein content, however, showed 
      an alternate pattern of response, decreasing to 87% of control at 10 microM CQ 
      but increasing to 125% of control at 30 microM. Histologic evaluation revealed 
      that the cytoplasm of the VYS endoderm epithelium was distended due to 
      vacuolization produced by CQ exposure. In the embryo proper, CQ inhibited cranial 
      neural tube development and altered the morphology of cranial neural crest cells. 
      These observations document the in vitro embryotoxicity of CQ and suggest altered 
      VYS histiotrophic nutrition as well as direct embryonic effects as possible 
      mechanisms of CQ embryotoxicity.
FAU - Ambroso, J L
AU  - Ambroso JL
AD  - Department of Environmental and Industrial Health, University of Michigan, Ann 
      Arbor 48109.
FAU - Harris, C
AU  - Harris C
LA  - eng
GR  - ES 05235/ES/NIEHS NIH HHS/United States
GR  - ES 07062/ES/NIEHS NIH HHS/United States
GR  - HD18258/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Teratology
JT  - Teratology
JID - 0153257
RN  - 0 (Proteins)
RN  - 886U3H6UFF (Chloroquine)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Abnormalities, Multiple/*chemically induced/pathology
MH  - Animals
MH  - Chloroquine/*toxicity
MH  - DNA/metabolism
MH  - Embryo, Mammalian/*drug effects/metabolism/pathology
MH  - Embryonic and Fetal Development/drug effects
MH  - Gestational Age
MH  - In Vitro Techniques
MH  - Proteins/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Yolk Sac/blood supply/drug effects
EDAT- 1993/09/01 00:00
MHDA- 1993/09/01 00:01
CRDT- 1993/09/01 00:00
PHST- 1993/09/01 00:00 [pubmed]
PHST- 1993/09/01 00:01 [medline]
PHST- 1993/09/01 00:00 [entrez]
AID - 10.1002/tera.1420480305 [doi]
PST - ppublish
SO  - Teratology. 1993 Sep;48(3):213-26. doi: 10.1002/tera.1420480305.