 the present study examines the dose - response relationship for 2,3,7,8-tetrachlorodibenzo - p - dioxin ( tcdd ) promotion of histologic and biochemical parameters by using a two - stage model for hepatocarcinogenesis in female sprague - dawley rats initiated with a single intraperitoneal dose of 175 mg of diethylnitrosamine ( den)/kg body weight at 70 days of age . starting 2 weeks after initiation 
 , treatment groups of 8 - 10 rats were given tcdd by gavage in corn oil once every 2 weeks for 30 weeks . 
 doses were 3.5 , 10.7 , 35.7 , and 125 ng tcdd / kg body weight / day . 
 a significant body weight reduction was present in the noninitiated group that received 125 ng tcdd . 
 relative liver weight was statistically increased in initiated rats treated with > or = 10.7 ng tcdd and in noninitiated rats treated with > or = 35.7 ng tcdd . 
 histopathologic evidence of cytotoxicity was dose - related in all tcdd - treated groups . 
 there was a statistically significant dose response in the bromodeoxyuridine ( brdu ) s - phase labeling index ( li ) in the den - initiated rats ( p < 0.01 ) and a marginally significant trend in the saline - treated rats ( p = 0.10 ) , but proliferating cell nuclear antigen s - phase li and growth fraction within altered hepatic foci showed no increase . among the den - initiated groups 
 there was a significant increase in glutathione s - transferase altered hepatic foci stereological parameters in the 125 ng tcdd group . 
 this study demonstrates that dose - response relationships for tcdd 's effects on cell proliferation growth of altered hepatic foci are different from previously reported effects on p450 gene expression , indicating that different biological or biochemical responses may exhibit different dose - response relationships.(abstract truncated at 250 words)imagesfigure 1.figure 1.figure 1.figure 1.figure 1.figure 2.figure 3.figure 4.figure 5.figure 6.figure 7 . 
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