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International Journal of Toxicology
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Target Organ Specificity: Diethylnitrosamine-and Dibenzylnitrosamine-induced Single-strand Breaks Plus Alkali-labile Bonds

Douglas E. Brash

National Center for Toxicological Research (HFT-1) Jefferson, AR 72079

Cheng M. Su

National Center for Toxicological Research (HFT-1) Jefferson, AR 72079

Hani A. Nabi

National Center for Toxicological Research (HFT-1) Jefferson, AR 72079

Kathleen S. Reuter

National Center for Toxicological Research (HFT-1) Jefferson, AR 72079

Judith Ortman

National Center for Toxicological Research (HFT-1) Jefferson, AR 72079

Yunis Sheikh

National Center for Toxicological Research (HFT-1) Jefferson, AR 72079

Ronald W. Hart

National Center for Toxicological Research (HFT-1) Jefferson, AR 72079

Quantitative dose response measurements of diethylnitrosamine-and dibenzylnitrosamine-induced DNA single-strand breaks plus alkali-labile bonds (SSB + ALB) (single-strand breaks, apurinic/apyrimidinic sites, and phosphotriesters) were performed on samples of 100,000 nuclei from Sprague-Dawley rats. Twenty-four hours after diethylnitrosamine injection, there were no SSB + ALB in brain (nontarget), SSB + ALB in kidney (target), and SSB + ALB in liver (target only after partial hepatectomy, tumor promoters, or chronic administration). Seven days after diethylnitrosamine injection, liver SSB + ALB had declined. The noncarcinogenic diethylnitrosamine analog, dibenzylnitrosamine, induced no SSB + ALB at 6 hours or 7 days postinjection. Induction of DNA damage, therefore, correlates well with target organ specificity of tumorigenesis when specificity is broadened to include those organs that exhibit tumors only when DNA damage is followed by additional treatments.

International Journal of Toxicology, Vol. 3, No. 2, 207-216 (1984)
DOI: 10.3109/10915818409018034
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