Differential induction of DNA strand breaks by nitrosamines in the rat liver and esophagus.
Hepatic and esophageal nuclei were isolated from Sprague-Dawley rats treated with 5 mg/kg dimethylnitrosamine (DMN), 100 mg/kg diethylnitrosamine (DEN) and 2.5 mg and 10 mg/kg methylbenzylnitrosamine (MBN) and subjected to alkaline elution to determine DNA strand breaks and their subsequent repair. Results obtained showed that hepatic nuclei isolated from rats 4 h after treatment by either DMN or DEN had about 60% of the DNA eluting through the filter. However, at 12 h post treatment, while about 50% of the single-strand breaks in dimethylnitrosamine treated rats were repaired, only about 10-15% of such breaks induced by DEN were repaired in the liver. That DEN is a more effective inducer of hepatic preneoplastic lesions could thus be attributed to this slow repair of the DEN induced lesions. Strand breaks were neither induced by DMN in the esophagus nor by MBN in the liver, the nontarget tissues. More surprising, however, was the finding that MBN induced little or no single-strand breaks in its target tissue, the esophagus. Furthermore, there was no evidence for DNA-protein cross-linking or alkali labile sites in the esophageal DNA. The results indicate that DNA damage induced by the initiating carcinogen in the target tissue may not necessarily involve strand breaks.
Mufti
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SI
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona Health Sciences Center, Tucson 85721.
Sipes
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IG
D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D004947:Esophagus / Q000187:drug effects*; D008099:Liver / Q000187:drug effects*; D008297:Male; D009602:Nitrosamines / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D009602:Nitrosamines