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.
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 microgram/kg/week in corn oil (5 ml/kg)] to the animals for up to 6 months. No exposure-related 32P-labeled spots indicative of TCDD or 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.
Randerath
K
K
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.
Putman
K L
KL
Randerath
E
E
Mason
G
G
Kelley
M
M
Safe
S
S
D000375:Aging / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004147:Dioxins / Q000633:toxicity*; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D009928:Organ Specificity; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; C051452:1,2,3,7,8-pentachlorodibenzo-p-dioxin; D004247:DNA