Short-term effects of the tumor promoting polychlorinated biphenyl mixture, Aroclor 1254, on I-compounds in liver, kidney and lung DNA of male Sprague-Dawley rats.
The effects of a tumor promoting polychlorinated biphenyl mixture, Aroclor 1254, on I-compounds (tissue, species and sex dependent DNA modifications that increase with age in untreated rodents) were studied by 32P-postlabeling in male Sprague-Dawley rat liver, kidney, and lung DNA. Aroclor 1254 was dissolved in corn oil and intraperitoneally (i.p.) injected (2 x 500 mg/kg, 2 weeks apart) into 3-month-old rats. Control rats were given corn oil. Groups of 3 animals were sacrificed at 2 and 6 weeks after the second injection of corn oil or Aroclor 1254. At both time points Aroclor 1254-treated rats had significantly lower body weights and higher liver weights while kidney and lung weights were unaffected. Thymidine incorporation into liver and lung DNA was significantly increased at both time points, while kidney DNA showed a small decrease at 2 weeks. Treatment resulted in significant reductions (ranging from 29 to 100%) of each of nine liver I-spots at 2 and 6 weeks. In treated rats there was no decrease in kidney I-spots at 2 weeks, while the levels of only two out of ten kidney spots were reduced by 42-91% at 6 weeks. At 2 weeks three out of seven and at 6 weeks four out of seven lung I-spots were lowered by 51-100% in the Aroclor 1254-treated rats. Thus the effects decreased in the order liver greater than lung greater than kidney. Since Aroclor 1254 has been reported to be a tumor promoter in liver and lung but not kidney, these results suggest a correlation between organ specific promotion of carcinogenesis by Aroclor 1254 and the reduction of DNA I-compounds.
Nath
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RG
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.
Randerath
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Randerath
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D000818:Animals; D001140:Aroclors / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000494:pharmacology*; D020111:Chlorodiphenyl (54% Chlorine); D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013936:Thymidine / Q000378:metabolism
D001140:Aroclors; D002273:Carcinogens; D020111:Chlorodiphenyl (54% Chlorine); D004247:DNA; D013936:Thymidine