In vivo replication of hepatic deoxyribonucleic acid of rats treated with dimethylnitrosamine: presence of dimethylnitrosamine-induced O6-methylguanine, N7-methylguanine, and N3-methyladenine in the replicated hybrid deoxyribonucleic acid.

Experiments were designed to determine whether some chemical lesions such as O6-methylguanine, N7-methylguanine, and N3-methyladenine induced in rat liver DNA by the hepatocarcinogen dimethylnitrosamine permit replication in vivo. For this purpose, [14C]dimethylnitrosamine was administered to methylate the parental strand of liver DNA. Four hours later, a time period when the carcinogen cannot be detected in either the liver or the blood, rats were subjected to partial hepatectomy in order to induce DNA replication. During the S phase, 5-bromo-2-deoxyuridine was administered to render the newly made strands heavy. The rebanded, hybrid, hepatic DNA of density 1.714 g/cm3 and greater was pooled from the neutral cesium chloride gradient, dialyzed, and lyophilized. The hybrid DNA was then treated with S1 nuclease to digest any single-stranded regions. The results obtained indicated the presence of O6-methylguanine, N7-methylguanine, and N3-methyladenine in S1 nuclease resistant, hybrid DNA. The results are interpreted to indicate that these chemical lesions permitted in vivo DNA replication.

[1]  E. Schwartz,et al.  Quantitative and qualitative aspects of the binding of N-hydroxy-2-acetylaminofluorene to hepatic chromatin fractions. , 1979, Chemico-biological interactions.

[2]  B. Strauss,et al.  Sites of inhibition of in vitro DNA synthesis in carcinogen- and UV-treated Φ174 DNA , 1979, Nature.

[3]  S. Rajalakshmi,et al.  Studies on carcinogen chromatin--DNA interaction: inhibition of N-methyl-N-nitrosourea-induced methylation of chromatin--DNA by spermine and distamycin A. , 1978, Biochemistry.

[4]  D. Sarma,et al.  Initiation of chemical carcinogenesis requires cell proliferation , 1978, Nature.

[5]  P. M. Rao,et al.  Carcinogen induced alterations in DNAase I release of N3-methyladenine from liver chromatin. , 1978, Chemico-biological interactions.

[6]  M. Radman,et al.  Mechanism of ultraviolet-induced mutagenesis: extent and fidelity of in vitro DNA synthesis on irradiated templates. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[7]  V. Craddock,et al.  De novo and repair replication of DNA in liver of carcinogen-treated animals. , 1978, Cancer research.

[8]  E. Miller.  Some current perspectives on chemical carcinogenesis in humans and experimental animals: Presidential Address. , 1978, Cancer research.

[9]  P. Caillet-Fauquet,et al.  Molecular mechanisms of induced mutagenesis. Replication in vivo of bacteriophage phiX174 single-stranded, ultraviolet light-irradiated DNA in intact and irradiated host cells. , 1977, Journal of molecular biology.

[10]  R. Harvey,et al.  Mechanism of phage phiX174 DNA inactivation by benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[11]  M. Wilhelm,et al.  Non-random binding of a chemical carcinogen to the DNA in chromatin. , 1977, Biochemical and biophysical research communications.

[12]  B. Gumbiner,et al.  Binding of N-hydroxy acetylaminofluorene to eu- and heterochromatin fractions of rat liver in vivo. , 1977, Cancer letters.

[13]  J. Popp,et al.  Inhibition of dimethylnitrosamine-induced strand breaks in liver DNA and liver cell necrosis by diethyldithiocarbamate. , 1977, Journal of the National Cancer Institute.

[14]  S. Rajalakshmi,et al.  Non-random nature of in vivo interaction of 3H-N-hydroxy-2-acetylaminofluorene and its subsequent removal from rat liver chromatin-DNA. , 1976, Chemico-biological interactions.

[15]  R. Setlow,et al.  Enhancement of postreplication repair in Chinese hamster cells. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[16]  S. Rajalakshmi,et al.  Nonrandom nature of in vivo methylation of dimethylnitrosamine and the subsequent removal of methylated products from rat liver chromatin DNA. , 1976, Cancer research.

[17]  B. Strauss,et al.  A model for replication repair in mammalian cells. , 1976, Journal of molecular biology.

[18]  G. Margison,et al.  Heterogeneous distribution of DNA alkylation products in rat liver chromatin after in vivo administration of N,N-di[14C]methylnitrosamine. , 1975, Chemico-biological interactions.

[19]  R. Wiegand,et al.  Specificity of the S1 nuclease from Aspergillus oryzae. , 1975, The Journal of biological chemistry.

[20]  S. Rajalakshmi,et al.  Replication of hepatic DNA in rats treated with dimethylnitrosamine. , 1975, Chemico-biological interactions.

[21]  G. W. Harrington,et al.  Determination of dimethylnitrosamine and nitrosoproline by differential pulse polarography. , 1975, Analytical chemistry.

[22]  R. Wu,et al.  Specific hydrolysis of the cohesive ends of bacteriophage lambda DNA by three single strand-specific nucleases. , 1975, The Journal of biological chemistry.

[23]  T. Kakunaga.  Requirement for cell replication in the fixation and expression of the transformed state in mouse cells treated with 4‐nitroquinoline‐1‐oxide , 1974, International journal of cancer.

[24]  A. Ganesan.  Persistence of pyrimidine dimers during post-replication repair in ultraviolet light-irradiated Escherichia coli K12. , 1974, Journal of molecular biology.

[25]  V. Craddock.  The pattern of methylated purines formed in DNA of intact and regenerating liver of rats treated with the carcinogen dimethylnitrosamine. , 1973, Biochimica et biophysica acta.

[26]  V. Vogt.  Purification and further properties of single-strand-specific nuclease from Aspergillus oryzae. , 1973, European journal of biochemistry.

[27]  K. Shishido,et al.  Estimation of the double-helical content in various single-stranded nucleic acids by treatment with a single strand-specific nuclease. , 1972, Biochimica et biophysica acta.

[28]  P. D. Lawley,et al.  Methylation of ribonucleic acid by the carcinogens dimethyl sulphate, N-methyl-N-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine. Comparisons of chemical analyses at the nucleoside and base levels. , 1972, The Biochemical journal.

[29]  A. Lehmann.  Postreplication repair of DNA in ultraviolet-irradiated mammalian cells. , 1972, Journal of molecular biology.

[30]  R. Hewitt,et al.  Influence of ultraviolet irradiation on chromosome replication in ultraviolet-sensitive bacteria. , 1971, Journal of molecular biology.

[31]  C. Wilde,et al.  Exchanges between DNA strands in ultraviolet-irradiated Escherichia coli. , 1971, Journal of molecular biology.

[32]  R. Bates,et al.  Replication of DNA after binding of the carcinogen 7,12-dimethylbenz [a] anthracene. , 1970, Journal of the National Cancer Institute.

[33]  P. Howard-Flanders,et al.  Discontinuities in the DNA synthesized in an excision-defective strain of Escherichia coli following ultraviolet irradiation. , 1968, Journal of molecular biology.

[34]  H. Green,et al.  Cell growth and the initiation of transformation by SV40. , 1966, Proceedings of the National Academy of Sciences of the United States of America.

[35]  T. Ando.  A nuclease specific for heat-denatured DNA in isolated from a product of Aspergillus oryzae. , 1966, Biochimica et biophysica acta.

[36]  A. Pegg,et al.  Formation and metabolism of alkylated nucleosides: possible role in carcinogenesis by nitroso compounds and alkylating agents. , 1977, Advances in cancer research.

[37]  A. Pegg,et al.  Molecular Mechanisms of Chemical Carcinogenesis , 1975 .

[38]  B. Singer.  The chemical effects of nucleic acid alkylation and their relation to mutagenesis and carcinogenesis. , 1975, Progress in nucleic acid research and molecular biology.

[39]  L. Sachs,et al.  The number of cell generations required to fix the transformed state in X-ray-induced transformation. , 1968, Proceedings of the National Academy of Sciences of the United States of America.

[40]  R. Setlow,et al.  Effects of ultraviolet radiation on macromolecular synthesis in Escherichia coli. , 1966, Journal of molecular biology.

[41]  G. Higgins,et al.  Experimental pathology of the liver , 1931 .