The Role of Endogenous Catechol Quinones in the Initiation of Cancer and Neurodegenerative Diseases

Abstract

Publisher Summary This chapter explores the role of endogenous catechol quinones in the initiation of cancer and neurodegenerative diseases. Several lines of evidence point to the major role of endogenous catechol quinones in the etiology of cancer and neurodegenerative diseases. The role of catechol estrogen-3,4-quinones in the initiation of breast cancer is very clear. The rapidly-depurinating N3Ade adducts result in a burst of apurinic sites that overwhelm the repair machinery of the cell and generate tumorigenic mutations by error-prone repair. In contrast, repair of the apurinic sites that are formed by the slow depurination of N7Gua adducts can proceed correctly and leads to very few mutations. Mutations at Ade bases accumulate in breast cancer cells, presumably through this mechanism. This pathway of activation for endogenous estrogens is mirrored by the activation of the synthetic estrogens hexestrol and DES. Evolution of fundamental concepts and principles of chemical carcinogenesis are elaborated in this chapter. The chapter explains the mechanism of tumor initiation by PAHs. Formation of estrogen metabolites, conjugates and DNA adducts is described in the chapter. Imbalance in estrogen homeostasis and unifying mechanism of initiation of cancer by endogenous and synthetic estrogens are elaborated as well.