Abstract
The carcinogenic activities of the arylamines have been linked to the abilities of the target tissues to transform these agents to derivatives that are capable of reacting with nucleic acid. Thus, the O-esterification of arylhydroxylamines and arylhydroxamic acids has been related to the production of C8 substituted guanine adducts and the subsequent formation of tumors (King, 1985). An important objective of attempts to elucidate the molecular mechanisms involved in tumorigenesis is the exploration of the extent to which these adducts perturb the processing and function of the DNA. The distortion imposed on DNA structure by bulky adducts can be manifested by mutagenic responses and changes in the metabolic disposition of the DNA (Singer and Grunberger, 1983). We have approached these phenomena in two ways by use of extrachromosomal DNA in E. coli cells. C8 adducts of 2-aminofluorene or 4-aminobiphenyl, and their N-acetylated derivatives have been studied (Figure 1). Our objectives have been to develop systems that might be used for comparison of structural differences on the mutagenic effects of site-specific arylamine DNA adducts and the biochemical effects these adducts have on DNA metabolism. Randomly modified DNA has been used in experiments designed to explore the effects of randomly introduced adducts on the ability of these vectors to be replicated, as well as mutagenic consequences. Single, site specific adducts have been employed to determine their mutagenic potentials.
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King, C.M., Reid, T.M., Tamura, N., Gupta, P.K. (1990). Mutagenic and Biochemical Consequences of the Reaction of Arylamines with DNA. In: Howard, P.C., Hecht, S.S., Beland, F.A. (eds) Nitroarenes. Environmental Science Research, vol 40. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3800-4_8
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DOI: https://doi.org/10.1007/978-1-4615-3800-4_8
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