Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on bone in two rat strains with different aryl hydrocarbon receptor structures.
Polychlorinated dibenzo-p-dioxins (PCDDs) are highly toxic environmental contaminants, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent dioxin. Here, we studied the effects of TCDD on bone. Two rat strains, Han/Wistar (H/W) and Long-Evans (L-E), were used because they exhibit a 1000-fold sensitivity difference in acute lethality of TCDD, which difference is related to the aryl hydrocarbon receptor (AHR). TCDD inhibited the tibial growth dose dependently, the effect being manifested at lower doses in the more sensitive L-E strain. In H/W rats the effect of TCDD was seen only at the high dose of 170 microg/kg (p < 0.05), whereas in the sensitive L-E rats a significant reduction of bone growth was already seen at 1.7 microg/kg (p < 0.01). This reduction was caused by the smaller tibial size because the diaphyseal bone mineral density (BMD) did not change. The three-point bending breaking force of the tibia was significantly reduced in H/W rats at 170 microg/kg (p < 0.05), but tibial stiffness was lower already at the dose of 17 microg/kg (p < 0.05). In the sensitive L-E strain, both breaking force and stiffness were reduced at the dose of 17 microg/kg (p < 0.001). These results indicate that TCDD dose-dependently interferes with bone growth, modeling, and mechanical strength. The altered transactivation domain of AHR is associated with a lower sensitivity of bone to TCDD in H/W rats, suggesting that AHR plays a role in modulating the effects of dioxins on bone.
Jämsä
T
T
Department of Medical Technology, University of Oulu, Finland.
Viluksela
M
M
Tuomisto
J T
JT
Tuomisto
J
J
Tuukkanen
J
J
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004785:Environmental Pollutants / Q000494:pharmacology*; D005260:Female; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D013314:Stress, Mechanical; D013977:Tibia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D000469:Alkaline Phosphatase