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

K. Randerath, K. L. Putman, E. Randerath, G. Mason, M. Kelley, S. Safe

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2285-2289
Number of pages5
JournalCarcinogenesis
Volume9
Issue number12
DOIs
StatePublished - Dec 1988

ASJC Scopus subject areas

  • Cancer Research

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this