Cellular alterations and enhanced induction of cleft palate after coadministration of retinoic acid and TCDD

Journal Article · Thu Jun 15 04:00:00 EDT 1989 · Toxicology and Applied Pharmacology; (USA)

DOI:https://doi.org/10.1016/0041-008X(89)90011-2· OSTI ID:5477079

Abbott, B D; Birnbaum, L S ^[1]

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1. National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA)

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and retinoic acid (RA) are both teratogenic in mice. TCDD is a highly toxic, stable environmental contaminant, while RA is a naturally occurring form of vitamin A. Exposure to TCDD induces hydronephrosis and cleft palate, and exposure to RA induces limb defects and cleft palate. Teratology studies previously have shown that the incidence of clefting is higher after exposure to RA + TCDD than would be observed for the same doses of either compound given alone. This study examines the cellular effects which result in cleft palate, after po administration on gestation Day (GD) 10 or 12 of RA + TCDD in corn oil (10 ml/kg total volume). Exposure on GD 10 to 6 micrograms TCDD + 40 mg RA/kg inhibited early growth of the shelves and clefting was due to a failure of shelves to meet and fuse. This effect on mesenchyme was observed in previous studies to occur after exposure on GD 10 to 40 mg/kg RA alone, but not after TCDD alone. After exposure on GD 12 to 6 micrograms TCDD + 80 mg RA/kg, clefting was due to a failure of shelves to fuse after making contact, because the medial cells differentiated into an oral-like epithelium. This response was observed in previous studies to occur after exposure to TCDD alone, but RA alone on GD 12 resulted in differentiation toward nasal-like cells. The interaction between TCDD and RA results in RA-like clefting after exposure on GD 10 and TCDD-like clefting after exposure on GD 12, and this clefting occurs at higher incidences than would occur after the same levels of either agent alone. After exposure on either GD 10 or 12 to RA + TCDD, the programmed cell death of the medial cells does not occur, and these cells continue to express EGF receptors and to bind 125I-EGF. The effects of RA and TCDD may involve modulation of the cells responses to embryonic growth and differentiation factors.

• OSTI ID: 5477079
• Journal Information: Toxicology and Applied Pharmacology; (USA), Journal Name: Toxicology and Applied Pharmacology; (USA) Journal Issue: 2 Vol. 99:2; ISSN TXAPA; ISSN 0041-008X
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL TISSUES
ANIMALS
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
CARBOXYLIC ACID ESTERS
CELL DIFFERENTIATION
DAYS LIVING RADIOISOTOPES
DIOXIN
ELECTRON CAPTURE RADIOISOTOPES
EPITHELIUM
ESTERS
GROWTH FACTORS
HETEROCYCLIC COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
MICE
MITOGENS
NUCLEI
ODD-EVEN NUCLEI
ONTOGENESIS
ORAL ADMINISTRATION
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PREGNANCY
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RETINOIC ACID
RODENTS
SYNERGISM
TERATOGENESIS
TISSUES
TOXICITY
VERTEBRATES