Interferon inducers increase O6-alkylguanine-DNA alkyltransferase in the rat liver.
We investigated whether treatment with the interferon inducer polyinosinic-polycytidylic acid and other cytokines (interleukin-1, tumor necrosis factor) or the cytokine inducer lipopolysaccharide modified O6-alkylguanine-DNA alkyltransferase (AT) in rat liver. AT levels were determined in liver extracts using N-[3H]methyl-N-nitrosourea alkylated calf thymus DNA as substrate and an HPLC procedure to measure O6-methylguanine. Doses as low as 0.1 mg/kg i.p. of polyinosinic-polycytidylic acid caused a highly significant increase (P less than 0.01) in AT levels in the liver, evident either 24 or 48 h after treatment. Lipopolysaccharide at the dose of 80 micrograms/kg i.p. also induced AT whereas interleukin-1 (60 micrograms/kg) or tumor necrosis factor (60 micrograms/kg) were inactive. Treatment with human recombinant interferon alpha A/D caused a highly significant increase in AT levels, thus confirming the hypothesis that interferon was probably responsible for the observed effect. These results suggest a link between the immune response and DNA repair mechanisms.
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
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Bertini
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Coccia
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Pagani
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Marinello
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Salmona
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D'Incalci
D000818:Animals; D004790:Enzyme Induction; D004926:Escherichia coli; D007369:Interferon Inducers / Q000494:pharmacology*; D007370:Interferon Type I / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008780:Methyltransferases / Q000096:biosynthesis*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D011070:Poly I-C / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007369:Interferon Inducers; D007370:Interferon Type I; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D011070:Poly I-C