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.

[1]  A. Pegg,et al.  Mammalian O6-alkylguanine-DNA alkyltransferase: regulation and importance in response to alkylating carcinogenic and therapeutic agents. , 1990, Cancer research.

[2]  M. Sekiguchi,et al.  Expression and cloning of complementary DNA for a human enzyme that repairs O6-methylguanine in DNA. , 1990, Journal of molecular biology.

[3]  R. S. Foote,et al.  Isolation and structural characterization of a cDNA clone encoding the human DNA repair protein for O6-alkylguanine , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[4]  M. D’Incalci,et al.  Interferon inducers increase O6-alkylguanine-DNA alkyltransferase in the rat liver. , 1990, Carcinogenesis.

[5]  R. Larson,et al.  Heterogeneity of O6-alkylguanine-DNA alkyltransferase activity in peripheral blood lymphocytes: relationship between this activity in lymphocytes and in lymphoblastoid lines from normal controls and from patients with Hodgkin's disease or non-Hodgkin's lymphoma. , 1989, Cancer research.

[6]  S. Hecht,et al.  32P-postlabeling analysis of 1-nitropyrene-DNA adducts in female Sprague-Dawley rats. , 1989, Carcinogenesis.

[7]  G. Margison,et al.  Increased O6-alkylguanine alkyltransferase activity in Chinese hamster V79 cells following selection with chloroethylating agents. , 1988, Carcinogenesis.

[8]  P. Ghezzi,et al.  Depression of liver drug metabolism and increase in plasma fibrinogen by interleukin 1 and tumor necrosis factor: a comparison with lymphotoxin and interferon. , 1988, International journal of immunopharmacology.

[9]  G. Margison,et al.  Reduction of the toxicity and mutagenicity of alkylating agents in mammalian cells harboring the Escherichia coli alkyltransferase gene. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[10]  N. Berger,et al.  Comparison of O6-alkylguanine-DNA alkyltransferase activity based on cellular DNA content in human, rat and mouse tissues. , 1986, Carcinogenesis.

[11]  G. Margison,et al.  Mechanisms of carcinogenesis induced by alkylating agents. , 1985, Biochimica et biophysica acta.

[12]  M. Waterfield,et al.  Active site and complete sequence of the suicidal methyltransferase that counters alkylation mutagenesis. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[13]  V. Craddock,et al.  Repair and replication of DNA in rat and mouse tissues in relation to cancer induction by N-nitroso-N-alkyl-ureas. , 1984, Chemico-biological interactions.

[14]  P. Kleihues,et al.  O6-alkylguanine-DNA alkyltransferase activity in human brain and brain tumors. , 1984, Carcinogenesis.

[15]  P. Kleihues,et al.  DNA methylation by dimethylnitrosamine in the Mongolian gerbil (Meriones unguiculatus): indications of a deficient, noninducible hepatic repair system for O6-methylguanine. , 1983, Cancer research.

[16]  T. Lindahl,et al.  Suicide inactivation of the E. coli O6‐methylguanine‐DNA methyltransferase. , 1982, The EMBO journal.

[17]  G. Margison,et al.  Effects of carcinogens and partial hepatectomy upon the hepatic O6-methylguanine repair system in mice. , 1982, Carcinogenesis.

[18]  D. Swenson,et al.  A comprehensive quantitative analysis of methylated and ethylated DNA using high pressure liquid chromatography. , 1980, Carcinogenesis.

[19]  K. Renton,et al.  Effect of interferon inducing agents (polyriboinosinic acid . polyribocytidylic acid and tilorone) on the heme turnover of hepatic cytochrome P-450. , 1980, Molecular pharmacology.

[20]  J. Cairns,et al.  Quantitation of the adaptive response to alkylating agents , 1979, Nature.

[21]  K. Renton,et al.  Effects of polyribonoinosinic acid polyribocytidylic acid and a mouse interferon preparation on cytochrome P-450-dependent monooxygenase systems in cultures of primary mouse hepatocytes. , 1978, Molecular pharmacology.

[22]  P. Seglen.  Preparation of isolated rat liver cells. , 1976, Methods in cell biology.

[23]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.