TY - JOUR
T1 - Organ-specific effects of long term feeding of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 1,2,3,7,8-pentachlorodibenzo-p-dioxin on i-compounds in hepatic and renal DNA of female sprague-dawley rats
AU - Randerath, K.
AU - Putman, K. L.
AU - Randerath, E.
AU - Mason, G.
AU - Kelley, M.
AU - Safe, S.
N1 - Funding Information:
The financial support of the US Environmental Protection Agency and the Texas A&M University Institute of Biosciences and Technology is gratefully acknowledged. Research in the laboratory of K.R. was supported in part by USPHS grants CA32157 and CA43263 awarded by the National Cancer Institute.
PY - 1988/12
Y1 - 1988/12
N2 - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent hepatocarcinogen, and 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PCDD) on liver and kidney DNA of female Sprague-Dawley rats were investigated by 32P-post-labeling assay. The compounds were administered by gavage [1 μg/kg/week in corn oil (5 ml/kg)] to the animals for up to 6 months. No exposure-related 32P-labeled spots indicative of TCDDor PCDD covalent DNA adducts were noted on the chromatograms of kidney or liver DNA nucleotides from the rats exposed to the toxins for 2 and 6 months. Corn-oil treated control animals exhibited the characteristic tissue- and age-specific patterns of 32P-labeled I-spots in liver and kidney DNA which are associated with specific DNA modifications of unknown origin and function. Treatment with either TCDD or PCDD resulted in a substantial reduction of the levels of I-compounds in liver, a target organ for TCDD carcinogenesis. After 6 months of exposure to TCDD the reductions in the amounts of individual hepatic I-compounds ranged from 37 to 77% and decreased levels were also observed after 2 months of treatment. It was apparent that PCDD was not as effective as TCDD in reducing hepatic I-compound levels and this corresponded with the lower aryl hydrocarbon receptor binding activity of the former compound. In contrast, TCDD and PCDD did not cause any significant decrease of I-compounds in the kidney which is not a site of TCDD-mediated carcinogenicity in female Sprague-Dawley rats. Whether I-compound deficiency contributes to TCDD mediated hepatocarcinogenesis (e.g. by facilitating DNA replication) needs to be investigated.
AB - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent hepatocarcinogen, and 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PCDD) on liver and kidney DNA of female Sprague-Dawley rats were investigated by 32P-post-labeling assay. The compounds were administered by gavage [1 μg/kg/week in corn oil (5 ml/kg)] to the animals for up to 6 months. No exposure-related 32P-labeled spots indicative of TCDDor PCDD covalent DNA adducts were noted on the chromatograms of kidney or liver DNA nucleotides from the rats exposed to the toxins for 2 and 6 months. Corn-oil treated control animals exhibited the characteristic tissue- and age-specific patterns of 32P-labeled I-spots in liver and kidney DNA which are associated with specific DNA modifications of unknown origin and function. Treatment with either TCDD or PCDD resulted in a substantial reduction of the levels of I-compounds in liver, a target organ for TCDD carcinogenesis. After 6 months of exposure to TCDD the reductions in the amounts of individual hepatic I-compounds ranged from 37 to 77% and decreased levels were also observed after 2 months of treatment. It was apparent that PCDD was not as effective as TCDD in reducing hepatic I-compound levels and this corresponded with the lower aryl hydrocarbon receptor binding activity of the former compound. In contrast, TCDD and PCDD did not cause any significant decrease of I-compounds in the kidney which is not a site of TCDD-mediated carcinogenicity in female Sprague-Dawley rats. Whether I-compound deficiency contributes to TCDD mediated hepatocarcinogenesis (e.g. by facilitating DNA replication) needs to be investigated.
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U2 - 10.1093/carcin/9.12.2285
DO - 10.1093/carcin/9.12.2285
M3 - Article
C2 - 3191574
AN - SCOPUS:0024264520
SN - 0143-3334
VL - 9
SP - 2285
EP - 2289
JO - Carcinogenesis
JF - Carcinogenesis
IS - 12
ER -