Impairment of telomeric quadruple helix formation - A possible event involved in the carcinogenicity of aromatic amines from the thermodynamic point of view?
Occupational exposure to aromatic amines (in particular, benzidine, 2-naphthylamine, and possibly 1-naphthylamine) has been linked to the development of bladder cancer due to the "carcinogenicity" of these compounds. However, little detailed knowledge is currently available concerning the interaction between these molecules and human DNA which might explain subsequent neoplastic transformation. Telomeres are protective DNA-protein complexes at the ends of human chromosomes which are functionally implicated in the maintenance of the chromosomal structural integrity. Telomeric DNA is composed of noncoding guanine-rich tandem sequences. Since covalent adduction of modified aromatic amines (protonated nitrenium ions) basically involves the nucleobase guanine, it appears reasonable to assume that telomeres represent the "hot spot" of the human DNA at which pertinent molecular interactions are likely to take place. Therefore, the present hypothesis focusses on thermodynamical aspects of possible molecular interactions between aromatic amines and telomeric DNA suggesting unfolding and destabilization of intramolecular telomeric quadruple helices inevitably accompanied by a loss of telomeric protective functions.
Gunia
Sven
S
Institute of Pathology, HELIOS Klinikum Bad Saarow, Charité-University Medicine Teaching Hospital, Pieskower Strasse 33, 15526 Bad Saarow, Germany. sven.gunia@helios-kliniken.de
D000588:Amines / Q000633:toxicity*; D015197:Carcinogenicity Tests; D006801:Humans; D016615:Telomere; D013816:Thermodynamics
D000588:Amines