2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an extremely potent environmental toxicant that is known to cause cancer and a host of other health problems at high exposures, but the larger and more pressing issue is whether TCDD represents a significant risk at prevailing environmental exposures. There is some evidence that even low maternal doses of TCDD can cause problems in tooth development, especially in breast-fed infants whose daily intake (per unit of body weight) of this toxicant from their mothers is known to be considerably higher than that for adults. This suggests that we can use tooth and mandible traits in a mouse model to detect subtle effects of TCDD exposure. The experimental plan for this detection, outlined below as two specific aims, involves testing this hypothesis by taking very specific morphometric measurements at several landmark points on the mandible and on the three molars (M1, M2, M3) in inbred, and Ahr congenic and null mice whose mothers have been dosed/not dosed with TCDD.
Specific Aim 1 : To assess interstrain variation in subtle effects of TCDD on mandible and tooth traits in mice. We will measure the overall size, shape, and asymmetry of the left and right mandibles and mandibular molar rows in the offspring of female mice treated/not treated with TCDD in each of six different inbred strains.
Specific Aim 2 : To determine the role of the Ahr locus in mediating TCDD's effects on mandible and tooth traits in mice. We will use mice congenic for the Ahr alleles b (""""""""sensitive"""""""" to TCDD effects) and d (less sensitive to TCDD effects) as well as null mice on a standard inbred background (C57BL/6) to test for differences in their response to the effects of TCDD on mandible and tooth traits. This preliminary information then will be used in a follow-up study aimed at identifying genes for these traits that are affected by TCDD. The identification of such genes should allow us to test for potential effects of this toxicant, even at prevailing levels of exposure in human populations, on a myriad of human diseases.
| Keller, James M; Zelditch, Miriam L; Huet, Yvette M et al. (2008) Genetic differences in sensitivity to alterations of mandible structure caused by the teratogen 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Pathol 36:1006-13 |
| Keller, James M; Huet-Hudson, Yvette; Leamy, Larry J (2008) Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on molar development among non-resistant inbred strains of mice: a geometric morphometric analysis. Growth Dev Aging 71:3-16 |
| Keller, James M; Huang, Johnny C; Huet-Hudson, Yvette et al. (2007) 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. Toxicology 242:52-62 |
| Keller, J M; Huet-Hudson, Y M; Leamy, L J (2007) Qualitative effects of dioxin on molars vary among inbred mouse strains. Arch Oral Biol 52:450-4 |
