Study On The Induction Of AHR And CYP1A1 Gene, Lipid Peroxidation, Ultrastructural Changes In SD Rat Livers Caused By TCDD

Objective2, 3, 7, 8- tetrachlorodibenzo-p-dioxin (TCDD), as the most toxic compounds, not only have severe harm to workers through occupational exposure but also have harm to ordinary people through living exposure. It is one of the hot spot to study now. Although great achievements have been gained on the study of TCDD, the toxic mechanism of TCDD is not fully clear yet. The goal of this experiment is to study the toxic mechanism of TCDD through studing the cytochrome p4501Al (CYP1A1) gene induction, aryl hydrocarbon receptor (AHR) gene induction,the lipid peroxidation and the changes of ultrastructure in livers of SD rats after treated with TCDD.MethodsThe female SD rats were treated with different doses ( 24h group:0, 0.01,0. 1,1, 10,50 u g/Kg body weight ;72h group:0, 0. 1, 1, 10 wg/Kg body weight) of TCDD for one timed, p. ). After 24h and/or 72h, thefollowing items were observed: 1. After 24h,the CYP1A1 and AHR gene expression in livers of SD rats ; 2.After 24h and 72h, the lipid peroxidation (SOD, GST, MDA) to livers of SD rats; 3. After 24h and 72h, the changes of ultrastructure in livers of SD rats.Resultsl.The ultrastructure of the livers: Mitochondrial dissolved, the particle of rough endoplasmic reticulum(RER) disappeared, RER pool dissolved, smooth endoplasmic reticulum(SER) pool enlarged and inosculated, chromatin agglomerated or dissolved, fatty drops formed, death of cell,the chromatin of Kupffer' s cell agglomerated, organelles dissolved slightly and the 72h group is severer than the 24h group.2. After treated with TCDD for 24 h,the activity of SOD decreased in all TCDD-treated groups but no significant differences to the control group; the activity of GST increased in all TCDD-treated groups but only the 50 u g/kg body weight group had significant difference to the control group(p<0. 05)and there were dose-response relationship between the TCDD dose and the activity of GST;the quantities of MDAincreased in all TCDD-treated groups but only the 10 and 50 u g/kg body weight groups had significant difference to the control group(p< 0.05)and there were dose-response relationship between the TCDD dose and the quantities of MDA. After treated with TCDD for 72 h, the activity of SOD decreased significantly in all TCDD-treated groups (p<0. 05) and there were dose-response relationship between the TCDD dose and the activity of SOD;the activity of GST increased in all TCDD-treated groups but no significant difference to the control group;the quantities of MDA increased in all TCDD-treated groups but only the 1 and 10u g/kg body weight group had significant difference to the controls (p<0. 05)and there were dose-response relationship between the TCDD dose and the quantities of MDA.3. Compared with the control group, the AHR gene expression increased in all TCDD-treated groups but only in the 50u g/kg body weight group had significant difference to control group(p<0. 05)and there were dose-response relationship between the TCDD dose and AHR gene expression. The CYP1A1 gene expression increased in all of TCDD-treated groups, except for the 0. 01 u g/kg body weight group. All of the groups had significant difference to control group(p<0. 05 or0. 01) and there were dose-response relationship between the TCDD dose and CYPlAl gene expression.Conclusion1. TCDD can cause the change of ultrastructure of female SD rat liver after treated with TCDD for 24 h and 72h. Chromatin is the target of TCDD to affect. TCDD can damage both hepatic cell and Kupffer' s cell.2. TCDD can cause hepatic lipid peroxidation of SD rats. The quantity of MDA increased,the activity of SOD decreased and the activity of GST could be induced but the induction ability was not strong.3. After treated with TCDD for 24 h, both of the AHR gene and the CYPlAl gene could be induced but the induction ability had differences. CYPlAl gene can be induced in low dose(0. In g/Kg body weight) but AHR gene could be induced only in high dose(50u g/Kg body weight).