In order to clarify to medchanisms of toxiceffects and tumor induction by DDT,we conducted a 2-year feeding study of p,p'-DDT in F344 rats at doses of 5,50,and 500 ppm,Investigations on toxicokinetics,hematology,b...In order to clarify to medchanisms of toxiceffects and tumor induction by DDT,we conducted a 2-year feeding study of p,p'-DDT in F344 rats at doses of 5,50,and 500 ppm,Investigations on toxicokinetics,hematology,biochemistry and histopathology were performed after 26,52,78,and 104 weeks.In addition,potential factors involved in hepatocarcinogenesis were examined.Both sexes at 500ppm showed tremor,body weight depression,anemia,microsomal enzyme induction,and increases in hepatic tumors.The concentrations of DDT and its metabolites in the liver tended to be higher in males,while those in the brain and plasma were higher in females,which might contribute to sex differences in toxic effects and tumor induction.DDT was found to inhibit intercellular communication and to produce oxidative stress secondary to metabolic activation in the liver.The oxidative stress may be a key factor in hepatocarcinogenesis by DDT.Microarray analysis of hepatic lesions is now underway.展开更多
文摘In order to clarify to medchanisms of toxiceffects and tumor induction by DDT,we conducted a 2-year feeding study of p,p'-DDT in F344 rats at doses of 5,50,and 500 ppm,Investigations on toxicokinetics,hematology,biochemistry and histopathology were performed after 26,52,78,and 104 weeks.In addition,potential factors involved in hepatocarcinogenesis were examined.Both sexes at 500ppm showed tremor,body weight depression,anemia,microsomal enzyme induction,and increases in hepatic tumors.The concentrations of DDT and its metabolites in the liver tended to be higher in males,while those in the brain and plasma were higher in females,which might contribute to sex differences in toxic effects and tumor induction.DDT was found to inhibit intercellular communication and to produce oxidative stress secondary to metabolic activation in the liver.The oxidative stress may be a key factor in hepatocarcinogenesis by DDT.Microarray analysis of hepatic lesions is now underway.