| Co-Investigator(Kenkyū-buntansha) |
HORIE Akio Univ.of Occupa. and Environ. Health, School of Medicine, Professor, 医学部, 教授 (80122852)
HANDA Sumio Kyushu Univ., Faculty of Medicine, Associate Professor, 医学部, 助教授 (50037503)
KIYOHARA Chikako Kyushu Univ., Faculty of Medicine, Research Assistant, 医学部, 助手 (00169963)
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| Keywords | 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) / 2,3,4,7,8-Pentachlorodibenzofuran(PenCDF) / Ah genotype / Ah responsiveness / Aryl hydrocarbon hydroxylase(AHH) / Mechanism of toxicity / Mouse |
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| Research Abstract |
In order to evaluate in more detail the segregation of the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) or 2,3,4,7,8-pentachloro dibenzofuran(PenCDF) with the Ah genotype, we used three inbred strains of mice chosen from each of the Ah responsive and nonresponsive ones.
TCDD and PenCDF were intraperitoneally administered to the six strains of mice in doses of 20ug/kg and 60 ug/kg, respectively, once every two weeks (6 times), three days after the last treatment, the animals were killed and then we examined the toxicity caused by TCDD or PenCDF by using several toxicological indices. Experimental data were analyzed for for the involvement of the Ah genotype in their toxicity and results obtained were as follows : 1. Changes in the weight of the liver and thymus after TCDD treatment showed higher correlation with the Ah responsiveness than those after the PenCDF treatment. 2. In aryl hydrocarbon hydroxylase (AHH) inducibility of the liver and lungs, we could not find any difference between the Ah responsive and nonresponsive strains. AHH inducibility, however, of the kidneys was much higher in the Ah responsive strains than in the Ah nonresponsive ones. 3. Histopathological changes in the liver due to TCDD or PenCDF seemed to be greater in the Ah responsive strains than in the Ah nonresponsive ones. We could not observe any hystopathological lesion attributable to the chemicals in other organs, including the kidneys. 4. Immunotoxicologic effect of TCDD or PenCDF and effect of the chemicals on the mitotic index did not necessarily correlate with the Ah genotype.
Based on the results described above, genetic regulations of the toxicity induced by TCDD or PenCDF seem not to be simple and we consider that some biological factors, including genes other than the Ah locus, are involved in the manifestations of the species and organ specific toxicity of the chemicals.
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