Electrophilic Theory, Metabolic Activation, and DNA Adducts

In the 1950-1960s Elizabeth and James Miller observed that a diverse array of chemicals could produce cancer in laboratory animals. In an attempt to explain this, 

TABLE 24.4. Major Evidence Supporting a Genetic Mechanism of Carcinogenesis 

Many carcinogens are or can be metabolized to electrophilic intermediates which can covalently bind to DNA. 

Autosomal dominant-inherited cancer syndromes provide direct evidence for a genetic component in the origin of cancer. 

Autosomal recessive-inherited cancer syndromes associated with chromosome fragility or decreased DNA repair predisposes affected individuals to cancer. 

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