O6-alkylguanine DNA alkyltransferase is induced by human recombinant interferon-alpha A/D in mouse liver.
Treatment of C57Bl or BALB/C mice with human interferon-alpha A/D (HuIFN-alpha A/D) significantly increased hepatic levels of the DNA repair enzyme O6-alkylguanine DNA alkyltransferase (AT). The maximum induction was seen 24 h after a single dose of 50-100 micrograms/kg IFN-alpha A/D. No induction was observed in rat liver hepatocytes cultured in vitro. Liver AT was also induced by poly(I:C), which is a potent IFN inducer. By increasing AT levels, IFN could protect against the potentially mutagenic alkylation at guanine O6 position caused by some carcinogens. Moreover this finding suggests a link between immune response and the DNA repair system, possibly acting in concert to defend the body from potentially toxic compounds.
Coccia
P
P
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Bertini
R
R
Pagani
P
P
Marinello
C
C
Taverna
P
P
Villa
P
P
D'Incalci
M
M
D000818:Animals; D004790:Enzyme Induction / Q000502:physiology; D005260:Female; D007370:Interferon Type I / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008780:Methyltransferases / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019853:O(6)-Methylguanine-DNA Methyltransferase; D011994:Recombinant Proteins
D007370:Interferon Type I; D011994:Recombinant Proteins; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase