The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on molar and mandible traits in congenic mice: a test of the role of the Ahr locus.
2,3,7,8-Tetracholorodibenzo-p-dioxin is a highly toxic substance that can cause a variety of adverse effects on organisms. While it has been shown that TCDD acts mainly through the aryl-hydrocarbon receptor (AHR), the mechanism of toxicity is not completely clear. To test the role of the AHR in mediating the effects of TCDD, we exposed two congenic strains of mice differing only at the Ahr locus (Ahr(b)/Ahr(b) and Ahr(d)/Ahr(d)) to TCDD (0, 0.01, 0, or 1 microg/kg body weight) in utero on gestation day 13 and examined the developmental effects on mandible and mandibular tooth row size and shape. Our hypothesis was that TCDD would significantly affect one or more of these endpoints in Ahr(b)/Ahr(b) mice, previously shown to be sensitive to the effects of TCDD, while causing little or no effect in mice carrying the less sensitive Ahr(d) allele. At the doses used in this study, TCDD did not alter the size of mandibles or molars in either Ahr(b)/Ahr(b) or Ahr(d)/Ahr(d) mice. However, we did find that the highest dose of TCDD altered mandible shape, but only in Ahr(b)/Ahr(b) (not Ahr(d)/Ahr(d)) male mice. Similarly, the highest dose of TCDD significantly altered molar shape in Ahr(b)/Ahr(b) but not Ahr(d)/Ahr(d) male mice, although females in both congenic strains were affected. These results suggest that the effects of TCDD on molar and mandible shape are influenced by the Ahr genotype but that males and females differ in sensitivity to both of these effects.
Keller
James M
JM
Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223-0001, USA. JMKeller@uncc.edu
Huang
Johnny C
JC
Huet-Hudson
Yvette
Y
Leamy
Larry J
LJ
D000014:Abnormalities, Drug-Induced; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005838:Genotype; D005865:Gestational Age; D008297:Male; D008334:Mandible / Q000002:abnormalities / Q000187:drug effects* / Q000254:growth & development; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008963:Molar / Q000002:abnormalities / Q000187:drug effects* / Q000254:growth & development; D009929:Organ Size; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012737:Sex Factors
D051792:Basic Helix-Loop-Helix Proteins; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; C484722:Ahr protein, mouse