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DNA Damage and Repair in Human Tissues pp 437–452Cite as

Alkylation Repair in Human Tissues

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Part of the book series: Basic Life Sciences ((BLSC,volume 53))

Abstract

The first evidence of alkylation of DNA by environmental chemicals was provided by Brookes and Lawley (1960, 1961) who showed that alkylating mustard gas formed 7-alkylguanine in nucleic acids; mustard gas was reported in 1946 (Auerbach and Robson) to be a chemical mutagen and respiratory tract tumours were observed among workers involved in its manufacture (Wada et al., 1968). The carcinogenicity of the alkylating nitrosamine dimethylnitrosamine (DMN) was first identified in the mid 1950s (Magee and Barnes, 1956) and in the subsequent decade the importance of DNA alkylation in the mutagenicity and carcinogenicity of such alkylating agents became apparent. The development of the thoughts underlying research on carcinogenic alkylating agents have been recently described in an interesting review by Lawley (1989).

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Abbreviations

7-medG:

7-methyldeoxyguanosine;

06-medG:

06-methyldeoxyguanosine;

3-meAde:

3-methyladenine;

04-meThy:

04-methylthymidine;

3-medG:

3-methyldeoxyguanosine;

06-meGua:

06-methylguanine;

7-meGua:

7-methylguanine

References

  • Auerbach, C. and Robson, J.M., 1946, Chemical production of mutations, Nature, 157: 302.

    Article  PubMed  CAS  Google Scholar 

  • Baker, S.J., Fearon, E.R., Nigro, J.M., Hamilton, S.R., Preisinger, A.C., Jessup, J.M., VanTuinen, P., Ledbetter, D.H., Barker, D.F., Nakamura, Y., White, R. and Vogelstein, B., 1989, Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas, Science, 244: 217–221.

    Article  PubMed  CAS  Google Scholar 

  • Barbacid, M., 1987, Ras genes, Ann. Rev. Biochem., 56: 779–827.

    Article  PubMed  CAS  Google Scholar 

  • Bartsch, H. and Montesano, R., 1984, Relevance of nitrosamines to human cancer, Carcinogenesis, 5: 1381–1393.

    Article  PubMed  CAS  Google Scholar 

  • Belinsky, S.A., White, C.M., Devereux, T.R., Swenberg, J.A., Anderson, M.W., 1987, Cell selective alkylation of DNA in rat lung following low dose exposure to the tobacco specific carcinogen 4-(N-methyl-N-nitrosamino)-l-(3-pyridyl)-1-butanone, Cancer Res., 47: 1143–1148.

    PubMed  CAS  Google Scholar 

  • Bishop, J.M., 1987, The molecular genetics of cancer, Science, 235: 305–311.

    Article  PubMed  CAS  Google Scholar 

  • Bos, J., 1988, The ras gene family and human carcinogenesis. Mutat. Res., 195: 255–271

    PubMed  CAS  Google Scholar 

  • Bos, J.L., 1989, ras oncogenes in human cancer: a review. Cancer Res., 49: 4682–4689

    PubMed  CAS  Google Scholar 

  • Boyle, J.M., Margison, G.P. and Saffhill, R., 1986, Evidence for the excision repair of O6-n-butyldeoxyguanosine in human cells, Carcinogenesis, 7: 1987–1990.

    Article  PubMed  CAS  Google Scholar 

  • Brent, T.P., 1986, Inactivation of purified human O6-alkylguanine-DNA alkyltransferase by alkylating agents or alkylated DNA, Cancer Res., 46: 2320–2323.

    PubMed  CAS  Google Scholar 

  • Brent, T.P., Dolan, M.E., Fraenkel-Conrat, H., Hall, J., Karran, P., Laval, F., Margison, G.P., Montesano, R., Pegg, A.E., Potter, P.M., Singer, B., Swenberg, J.A. and Yarosh, D.B., 1988, Repair of O-alkylpyrimi dines in mammalian cells: a present consensus, Proc. Natl. Acad. Sci. USA, 85: 1759–1762.

    Article  PubMed  CAS  Google Scholar 

  • Brookes, P. and Lawley, P.D., 1960, The reaction of mustard gas with nucleic acids in vitro and in vivo, Biochem J., 77: 478–484.

    PubMed  CAS  Google Scholar 

  • Brookes, P. and Lawley, P.D., 1961, The reaction of mono- and di-functional alkylating agents with nucleic acids, Biochem. J., 80: 496–503.

    PubMed  CAS  Google Scholar 

  • Dandekar, S., Sukumar, S., Zarbl, H., Young, L.J.T. and Cardiff, R.D., 1986, Specific activation of the cellular Harvey-ras oncogene in dimethylbenzanthracene-induced mouse mammary tumors. Molec. Cell. Biol., 6: 4104–4108.

    PubMed  CAS  Google Scholar 

  • Degan, P., Montesano, R. and Wild, C.P., 1988, Antibodies against 7-methyldeoxyguanosine: its detection in peripheral blood lymphocyte DNA and potential applications to molecular epidemiology, Cancer Res., 48: 5065–5071.

    PubMed  CAS  Google Scholar 

  • Dolan, M.E., Schicchitano, D. and Pegg, A.E., 1988, Use of oligodeoxynucleotides containing O6-alkylguanine for the assay of O6-alkylauanine-DNA-alkyltransferase activity, Cancer Res, 48: 1184–1188.

    PubMed  CAS  Google Scholar 

  • Ellison, K.S., Dogliotti, E., Connors, T.d., Basu, A.K. and Essigmann, J.M., 1989, Site-specific mutagenesis by O6-alkylguanines located in the chromosomes of mammalian cells: influence of the mammalian O6-alkylguanine-DNA alkyltransferase, Proc. Natl. Acad. Sci. USA, 86: 8620–8624.

    Article  PubMed  CAS  Google Scholar 

  • Foiles, P.G., Miglietta, L.M., Akerkar, S.A., Everson, R.B. and Hecht, S.S., 1988, Detection of O6-Methyldeoxyguanosine in human placental DNA, Cancer Res., 48: 4184–4188.

    PubMed  CAS  Google Scholar 

  • Gallagher, P. E. and Brent, T.P., 1984, Further purification and characterisation of human 3-methyladenine DNA glycosylase. Evidence for broad specificity, Biochem. Biophys. Acta., 782: 394–401.

    PubMed  CAS  Google Scholar 

  • Gerson, S.L., Trey, J.E., Miller, K. and Berger, N.A., 1986, Comparison of O6-alkylguanine-DNA alkyltransferase activity based on cellular DNA content in human, rat and mouse tissues, Carcinogenesis, 7: 745–749.

    Article  PubMed  CAS  Google Scholar 

  • Gombar, C.T., Katz, E.J., Magee, P.N. and Sirover, M.A., 1981, Induction of the DNA repair enzymes uracil DNA glycosylase and 3-methyladenine DNA glycosylase in regenerating rat liver, Carcinogenesis, 2: 595–599.

    Article  PubMed  CAS  Google Scholar 

  • Graves, R.J., Li, B.F.L. and Swann, P.F., 1987, in; “Relevance of N-Nitroso Compounds to Human Cancer: Exposures and Mechanisms” H. Bartsch, I.K. O’Neill, and R. Shulte-Hermann, eds., IARC Scientific Publications No. 84, pp 41–43, International Agency for Research on Cancer, Lyon.

    Google Scholar 

  • Hall, J., Brésil, H. and Montesano, R., 1985, O6-alkylguanine DNA alkyltransferase activity in monkey, human and rat liver, Carcinogenesis, 6: 209–211.

    Article  PubMed  CAS  Google Scholar 

  • Harris, A.L., Karran, P. and Lindahl, T., 1983, O6-Methylguamne-DNA methyltransferase of human lymphoid cells: structural and kinetic properties and absence in repair-deficient cells, Cancer Res., 43: 3247–3252.

    PubMed  CAS  Google Scholar 

  • Heilbronn, R., Schlehofer, J.R., Yalkinoglu, A.O. and Zur Hausen, H., 1985, Selective DNA-amplification induced by carcinogens (initiators): evidence for a role of proteases and DNA polymerase alpha. Int. J. Cancer, 36: 85–91.

    Article  PubMed  CAS  Google Scholar 

  • Helland, D.E., Male, R., Haukanes, B.I., Olsen, L., Haugan, I. and Kleppe, K., 1987, Properties and mechanism of action of eukaryotic 3-methyladenine-DNA glycosylases, J. Cell. Sci. Suppl. 6: 139–146.

    PubMed  CAS  Google Scholar 

  • Herron, D.C. and Shank, R.C., 1980, Methylated purine in human liver DNA after probable dimethylnitrosamine poisoning, Cancer Res., 40: 3116–3117.

    PubMed  CAS  Google Scholar 

  • Hollstein, M.C., Smits, A.M., Galiana, C., Yamasaki, H., Bos, J.L., Mandard, A., Partensky, C. and Montesano, R., 1988, Amplification of epidermal growth factor receptor gene but no evidence of ras mutations in primary human esophageal cancers, Cancer Res., 48: 5119–5123.

    PubMed  CAS  Google Scholar 

  • Huitfeldt, H.S., Sprangler, E.F., Hunt, J.M. and Poirier, M.C., 1988, Immunohistochemical localisation of DNA adducts in rat liver tissue and phenotypically altered foci during oral administration of 2-acetylaminofluorene, Carcinogenesis, 7: 123–129.

    Article  Google Scholar 

  • Jiang, W. et al, 1989, Rapid detection of ras oncogenes in human tumors: applications to colon, esophageal and gastric cancer. Oncogene, 4: 923–928.

    PubMed  CAS  Google Scholar 

  • Karran, P., 1985, Possible depletion of a DNA repair enzyme in human lymphoma cells by subversive repair, Proc. Natl. Acad. Sci. USA, 82: 5285–5289.

    Article  PubMed  CAS  Google Scholar 

  • Kumar, R. and Barbacid, M., 1988, Oncogene detection at the single cell level. Oncogene, 3: 647–651.

    PubMed  CAS  Google Scholar 

  • Laval, F. and Laval, J., 1984, Adaptive response in mammalian cells: cross reactivity of diferent pretreatments oncytotoxicity as contrasted to mutagenicity, Proc. Natl. Acad. Sci. USA, 81: 1062–1066.

    Article  PubMed  CAS  Google Scholar 

  • Lavi, S., 1981, Carcinogen-Omediated amplification of viral DNA sequences in simiabn virus 40-transformed Chinese hamster embryo cells, Proc. Natl. Acad. Sci. USA, 68: 6144–6148.

    Article  Google Scholar 

  • Lawley, P.D., 1989, Mutagens as carcinogens: development of current concepts. Mutat. Res., 213: 3–25.

    Article  PubMed  CAS  Google Scholar 

  • Lindahl, T., Sedgwick, B., Sekiguchi, M. and Nakabeppu, Y., 1988, Regulation and expression of the adaptive response to alkylating agents, Ann. Rev. Biochem., 57: 133–157.

    Article  PubMed  CAS  Google Scholar 

  • Lu, S.-H., Hsieh, L.-L., Luo, F.-C. and Weinstein, I.B., 1988, Amplification of the EGF receptor and c-myc genes in human esophageal cancers, Int. J. Cancer, 42: 502–505.

    Article  PubMed  CAS  Google Scholar 

  • Magee, P.H. and Barnes, J.M., 1956, The production of malignant primary hepatic tumors in the rat by feeding dimethylnitrosamine, Br. J. Cancer, 10: 114–122.

    Article  PubMed  CAS  Google Scholar 

  • Menkveld, G.J., Van der Laken, C.J., Hermsen, T., Kriek, E., Scherer, E. and Den Engelse, L., 1985, Immunohistochemical localization of O6-ethyldeoxy-guanosine and deoxyguanosin-8-yl-(acetyl)aminofluorene in liver sections of rats treated with diethylnitrosamine, ethyl nitrosourea or N-acetyl-aminofluorene, Carcinogenesis, 6: 263–270.

    Article  PubMed  CAS  Google Scholar 

  • Mironov, N.M., Wild, C.P., Martel-Planche, G., Swann, P.F. and Montesano, R., 1989, Measurement of the removal of O6-methylguanine and O4-methylthymine from oligodeoxynucleotides using an immunoprecipitation technique, Anal. Biochem., 183: 74–79.

    Article  PubMed  CAS  Google Scholar 

  • Mitra, G., Pauly, G.T., Kumar, R., Pei, G.K., Hughes, S.-H., Moschel, R.C. and Barbacid, M., 1989, Molecular analysis of 06-substituted guanine-induced mutagenesis of ras oncogenes, Proc. Natl. Acad. Sci. USA, 86: 8650–8654.

    Article  PubMed  CAS  Google Scholar 

  • Montesano. R., Brésil, H. and Margison, G.P., 1979, Increased excision of O6-methylguanine from rat liver DNA after chronic administration of dimethylnitrosamine, Cancer Res., 39: 1789–1802.

    Google Scholar 

  • Montesano, R., Brésil, H., Degan, P., Martel-Planche, G., Serres, M. and Wild, C.P., Detection in human cells of alkylated macromolecules attributable to exposure to nitrosamines, IARC Scientific Publications No. 89, Lyon, pp. 75–82.

    Google Scholar 

  • Morimoto, K., Dolan, M.E., Scicchitano, D. and Pegg, A.E., 1985, Repair of O6-propylguanine and O6-butylguanine in DNA by O6-alkylguanine-DNA alkyltransferases from rat liver and E. coli, Carcinogenesis, 6: 1027–1031.

    Article  PubMed  CAS  Google Scholar 

  • Myers, R.M., Maniatis, T. and Lehrman, L.S., 1987, Methods in Enzymol., 155: 501–527.

    Article  CAS  Google Scholar 

  • Nemoto, N., Nakatsuru, Y., Nakagawa, A. and Ishikawa, T., 1988, Immunohistochemical detection of anti(±)trans-7,8-dihydroxy-9,10-epoxy-7, 8, 9, 10-tetrahydrobenzo(a)pyrene-bound adduct in nuclei of cultured HeLa cells and mouse lung tissue, J. Cancer Res., Clin. Oncol., 114: 225–230.

    Article  CAS  Google Scholar 

  • Pegg, A.E. and Hui, G., 1978, Formation and subsequent removal of O6-methylguanine from deoxyribonucleic acid in rat liver and kidney after small doses of dimethylnitrosamine, Biochem. J., 173: 739–748.

    PubMed  CAS  Google Scholar 

  • Pegg, A.E., Wiest, L., Foote, R.S., Mitra, S. and Perry, W., 1983, Purification and propertis o O6-methylguanine-DNA transmethylase from rat liver, J. Biol. Chem., 258: 2327–2333.

    PubMed  CAS  Google Scholar 

  • Planche-Martel, Likhachev, A., Wild, C.P. and Montesano, R., 1985, Modulation of repair of O6-methylguanine in parenchymal and nonparenchymal liver cells of rats treated with dimethylnitrosamine, Cancer Res., 45: 4768–4773.

    PubMed  CAS  Google Scholar 

  • Preussmann, R., Spiegelhalder, B., Eisenbrand, G., and Janzowiski, C., 1979, N-Nitroso compounds in foods, in: Naturally Occurring Carcinogens, Mutagens and Modulators of Carcinogenesis, E.C. Miller, J.A. Miller, I. Hirono, T. Sugimura, and S. Takayama, eds., Japanese Scientific Societies Press, Tokyo, pp. 185–194.

    Google Scholar 

  • Saffhill, R., Margison, G.P. and O’Connor, P.J., 1985, Mechanisms of carcinogenesis induced by alkylating agents, Biochim. Biophys. Acta., 823: 111–145.

    PubMed  CAS  Google Scholar 

  • Saffhill, R., Badawi, A.F. and Hall, C.N., 1988, Detection of O6-methylguanine in human DNA, IARC Scientific Publications No. 89, 301–305.

    Google Scholar 

  • Sagher, D., Karrison, T., Schwartz, L., Larson, R., Meier, P. and Strauss, B., 1988, Low O6-alkylguanine DNA alkyltransferase activity in the peripheral blood lymphocytes of patients with therapy-related acute nonlymphocytic leukemia, Cancer Res., 48: 3084–3089.

    PubMed  CAS  Google Scholar 

  • Samson, L. and Cairns, J., 1977, A new pathway for DNA repair in Escherichia choli, Nature (Lond.), 267: 281–282.

    Article  PubMed  CAS  Google Scholar 

  • Samson, L., Thomale, J. and Rajewsky, M.F., 1988, Alternative pathways for the in vivo repair of 06-alkylguanine and 04-alkylthymine in Escheria coli: the adaptive response and nucleotide excision repair, EMBO J, 7: 2261–2267.

    PubMed  CAS  Google Scholar 

  • Schiestl, R., 1989, Non-mutagenic carcinogens induced intrachromosomal recombination in yeast, Nature, 337: 285–288.

    Article  PubMed  CAS  Google Scholar 

  • Scicchitano, D., Jones, R.A., Kuzmich, S., Gaffney, B., Lasko, D.D., Essigmann, J.M. and Pegg. A.E., 1986, Repair of oligodeoxy-nucleotides containing O6-methylguanine by O6-alkylguanine-DNA-alkyltransferase, Carcinogenesis, 7: 1383–1386.

    Article  PubMed  CAS  Google Scholar 

  • Singer, B. and Brent, T.P., 1981, Human lymphoblasts contain DNA glycosylase activity excising N-3 and N-7 methyl and ethyl purines but not O6-alkylguanines or 1-alkyladenines, Proc. Natl. Acad. Sci. USA, 78: 856–860.

    Article  PubMed  CAS  Google Scholar 

  • Singer, B. and Grunberger, D., 1983, “Molecular Biology of Mutagens and Carcinogens,” Plenum Press, New York & London.

    Book  Google Scholar 

  • Singer, G.M., Chuan, J., Roman, J., Min-Hsin Li and Lijinsky, W., 1986, Nitrosamines and nitrosamine precursors in foods from Linxian, China, a high incidence area for esophageal cancer, Carcinogenesis, 7: 733–736.

    Article  PubMed  CAS  Google Scholar 

  • Tsuda, T. et al, 1988, Amplification of the hst-1 gene in human esophageal carcinomas. Jpn. J. Cancer Res., 79: 584–588.

    Article  PubMed  CAS  Google Scholar 

  • Tsuda, T., Tahara, E., Kajiyama, G., Sakamoto, H., Terada, M. and Sugimura, T., 1989, High incidence of coamplification of hst-1 and int-2 genes in human esophageal carcinomas, Cancer Res., 49: 5505–5508.

    PubMed  CAS  Google Scholar 

  • Tsutsumi, M. et al., 1988, Coamplification of the hst-1 and int-2 genes in human cancers. Jpn. J. Cancer Res., 79: 428–432.

    Article  PubMed  CAS  Google Scholar 

  • Umbenhauer, D., Wild, C.P., Montesano, R., Saffhill, R., Boyle, J.M., Huh, N., Kirstein, U., Thomale, J., Rajewsky, M.F. and Lu, S.H., 1985, O6-Methyldeoxyguanosine in oesophageal DNA among individuals at high risk of oesophageal cancer, Int. J. Cancer, 36, 661–665.

    Article  PubMed  CAS  Google Scholar 

  • Waldstein, E.A., Cao., E.-H., Bender, M.A. and Setlow, R.B., 1982, Abilities of extracts of human lymphocytes to remove O6-methylguanine from DNA, Mut. Res., 95: 405–416.

    Article  CAS  Google Scholar 

  • Wada, S., Miyanashi, M., Nishimoto, Y., Kambe, S. and Miller, R.W., 1968, Mustard gas as a cause of respiratory neoplasia in man, Lancet, 1: 1161–1163.

    Article  PubMed  CAS  Google Scholar 

  • Wild, C.P., Stich, H.F. and Montesano, R., 1989, Presence of alkylated DNA in oral mucosal cells from cigarette smokers, Proc. Am. Assoc. Cancer Res., 30: 318.

    Google Scholar 

  • Wild, C.P., Montesano, R., Van Benthem, J., Scherer, E. and Den Engelse, L., 1990, Intercellular variation in aflatoxin B1 and G1 DNA adduct levels in rat tissues: a quantitative immunocytochemical study, J. Cancer Res. Clin. Oncol., in press.

    Google Scholar 

  • Wild, C.P. and Montesano, R., 1990a, Detection of alkylated DNA adducts in human tissues, in: Molecular Dosimetry of Human Cancer: Epidemiological, Analytical and Social Considerations, P.L. Skipper and J.D. Groopman, eds., Telford Press, in press

    Google Scholar 

  • Wild, C.P. and Montesano, R., 1990b, Evaluation of the immunological quantitation of human exposure to aflatoxins (AF) and N-nitrosamines (NNO) in epidemiological studies, in: Immunochemical Methods for Monitoring Human Exposure to Toxic Chemicals in Foods and the Environment, Pacifichem ’89, Marcel Dekker Inc., in press.

    Google Scholar 

  • Yarosh, D.B., 1985, The role of O6-methylguanine-DNA methyl transferase in cell survival, mutagenesis and carcinogenesis, Mutat. Res., 145: 1–16.

    PubMed  CAS  Google Scholar 

  • Yarosh, D.B., Rice, M., Day, R.S., Foote, R.S. and Mitra, S., 1984, O6-Methylguanine-DNA methyl transferase in human cells, Mutat. Res., 131: 27–36.

    PubMed  CAS  Google Scholar 

  • Yokota, J., Tsukada, Y., Nakajima, T., Gotoh, M., Shimosato, Y., Mori, N., Tsunokawa, Y., Sugimura, T. and Terada, M., 1989, Loss of heterozygosity on the short arm of chromosome 3 in carcinoma of the uterine cervix, Cancer Res, 49: 3598–3601.

    PubMed  CAS  Google Scholar 

  • Zarbl, H., Sukumar, S., Arthur, A.V., Martin-Zanca, D. and Barbacid, M., 1985, Direct mutagenesis of Ha-ras-1 oncogenes by N-nitroso-N-methylurea during initiation of mammary carcinogenesis in rats. Nature, 315: 382.

    Article  PubMed  CAS  Google Scholar 

  • Zur Hausen et al. (eds), 1987, The role of gene amplification in tumor initiation and promotion, Lippincott, New York.

    Google Scholar 

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Authors and Affiliations

  1. Unit of Mechanisms of Carcinogenesis, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372, Lyon Cedex 08, France

    R. Montesano, J. Hall, M. Hollstein, N. Mironov & C. P. Wild

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  1. R. Montesano
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  2. J. Hall
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  3. M. Hollstein
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  4. N. Mironov
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  1. Brookhaven National Laboratory, Upton, New York, USA

    Betsy M. Sutherland  & Avril D. Woodhead  & 

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Montesano, R., Hall, J., Hollstein, M., Mironov, N., Wild, C.P. (1990). Alkylation Repair in Human Tissues. In: Sutherland, B.M., Woodhead, A.D. (eds) DNA Damage and Repair in Human Tissues. Basic Life Sciences, vol 53. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0637-5_33

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  • DOI: https://doi.org/10.1007/978-1-4613-0637-5_33

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