Repair of DNA Adducts Produced by Alkylation

  • Bernard S. Strauss
Chapter

Abstract

Auerbach and Robson’s discovery (1942) that mustard gas is mutagenic was released after the close of the second World War (Auerbach and Robson, 1946, 1947) and quickly led to the finding that many simple alkylating agents are mutagenic. Some of these compounds were found to be useful in cancer chemotherapy because of their cytotoxic effect but, at the same time, were carcinogenic themselves, the ratio of therapeutic to carcinogenic activity varying mysteriously from compound to compound (see Whitelock, 1958). It was natural that the reactivity of these alkylating agents with cellular constituents should be investigated. The reactivity with protein was especially studied during the 1950’s because of the general biochemical importance of this class of compound. However, the gradual acceptance of the view that the genetic material is only DNA focused attention on alkylation of this substance. The reaction of alkylating agents with nucleic acid, particularly with DNA has therefore been extensively studied during the 1960’s and 1970’s for the theoretical reason that mutation must involve a change in DNA structure, rather than because of any direct demonstration that alkylation of DNA is uniquely important. Demonstration of the metabolic activation of hydrocarbon and other carcinogens to form electrophilic reagents with the reactivity characteristic of alkylating agents (Cramer et al., 1960; Miller et al., 1960) intensified the search for DNA adducts since this discovery made it likely that the initial reaction leading to carcinogenesis must be the formation of a covalently bound adduct, presumably to DNA.

Keywords

Excision Repair Alkylating Agent RAJI Cell Xeroderma Pigmentosum Human Peripheral Blood Lymphocyte 
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Copyright information

© Springer Science+Business Media New York 1976

Authors and Affiliations

  • Bernard S. Strauss
    • 1
  1. 1.Department of MicrobiologyThe University of ChicagoChicagoUSA

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