In vitro evolution of RNA aptamers recognizing carcinogenic aromatic amines.

The modification of cellular DNA by environmental substances is thought to be a crucial event in chemical induced carcinogenesis. Among the environmental carcinogens, aromatic amines are known for the fact that they can induce several types of cancers through the formation of so-called DNA adducts. We took advantage of the potential of the SELEX method to select for highly specific RNA ligands that recognize specific genotoxic aromatic amines.

Analyses of bulky DNA adduct levels in human breast tissue and genetic polymorphisms of cytochromes P450 (CYPs), myeloperoxidase (MPO), quinone oxidoreductase (NQO1), and glutathione S-transferases (GSTs).

Environmental carcinogens are converted into DNA-reactive metabolites by phase I and phase II enzymes that are involved in the activation and detoxification of xenobiotics. Several of these enzymes display genetic polymorphisms that alter their activity leading to individual variation in DNA damage levels and thus cancer susceptibility. We investigated the relationship between DNA adduct levels and genetic polymorphisms in key enzymes of chemical carcinogenesis: CYP1A1, CYP1A2, GSTT1, GSTM1, GSTP1, NQO1 and MPO.