| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
|---|
| Research Abstract |
Dioxins have a wide range of toxicity on mice and humans. The toxicities are the induction of detoxicification enzymes in the liver, reproductive toxicity, developmental toxicity, immunotoxicity, tumor promotion activity, and endocrine disrupting activity. This project has dealt with the pathogenesis of some of these toxicities.
When dams were administered with 40 micrograms TCDD/kg b.w. by gavage at gestation day (GD) 12.5, cleft palate and dilated renal pelvis were induced in fetuses at GD18.5. The pathogenesis of the cleft palate was revealed to be caused by the inhibition of secondary palatal shelves and to be mediated by the aryl hydrocarbon receptor (dioxin receptor). cDNA microarray was used to reveal the transcriptional changes at the mRNA level when cleft palte was induced. However, no conclusive data was obtained.
As for the male reproductive toxicity, dams were administered with 0, 0.625, 2.5, 10 micrograms TCDD/kg b.w. by gavage at GD 14.5. The newborns were nursed by the dams by 4 weeks, and killed at 10 weeks. Male reproductive organs were examined as to the histology of the testis, seminal vesicles, and prostate glands. Sperm in the epididymis was counted. However, I could not find any appropriate end points to evaluate the male reproductive toxicity.
Dioxin has effects also on the central nervous system. As a basic study, I examined the cerebellum with special reference to the developmental process. Behavioral teratological study was done after phenytoin was orally given to newborn mice. The technique developed here is expected to be applied to the evaluation of dioxin effect on the CNS.
|
