Studies on the interaction between Cd2+ ions and DNA

Cadmium is a potent carcinogen in rodents and has recently been accepted by the International Agency for Research on Cancer as a category 1 (human) carcinogen, but the molecular mechanism of its action remains largely unclear. It has however been suggested that 2 cadmium-induced carcinogenesis may involve either direct or indirect interaction of Cd2+ with DNA. Cd2+ is believed to bind covalently with N7 centres of adenine and guanine. At low concentrations (less than or equal to 50 mM), Cd2+ is found to react with plasmid DNA to produce a mixture of Form I and Form II bands whereas at higher concentrations (greater than or equal to100 mM), Cd2+ causes extensive damage to DNA at a pH 5.8 solution of cadmium nitrate. Within the range 0-100 mM (when pH is adjusted to 7.4 by adding NaOH) an increase in concentration of Cd2+ is found to cause a decrease in the gel mobility rate of plasmid and an increase in the intensity of the Form H band. When plasmid DNA is digested with BamH1. only the Form III band is observed both in the presence and absence of Cd2+. However, the mobility of the band is found to decrease with the increase in the concentration of Cd2+. When the enzyme Ssp1 which cuts plasmid DNA at the AT sites is used instead of BamH1, two bands are observed in the presence of cadmium as against one band in the absence of cadmium. These results suggest that Cd2+ binds covalently with DNA (possibly at G, A and T centres) and can form intrastrand bifunctional AT adducts but not the GG adducts. It may also be that neither GG nor AT adducts are formed and yet Ssp1 digestion is prevented because of a structural modification introduced in adenine by its interaction with Cd2+. In the presence of antioxidants such as cysteine, glutathione and ascorbate (especially cysteine and ascorbate), DNA damage is found to be greater than expected for the combined effects of the antioxidant and Cd2+. The increased DNA damage is believed to be due to the formation of reactive oxygen species (ROS). (C) 2002 Elsevier Science Inc. All rights reserved.