Paraquat induced DNA damage by reactive oxygen species

Abstract

The redox cycling contact herbicide paraquat (PQ) causes oxidative damage to pulmonary tissue. PQ is reduced enzymatically to PQ radical in lung where it reacts with molecular oxygen, generating reactive oxygen species (ROS). ROS damage various macromolecules including DNA. However, the ability of paraquat to mediate DNA damage is unknown. In this study, Bam H1 site (5'-GGATCC-3') on pBR322 DNA was chosen as the target sequence for a study of the PQ-mediated DNA damage. The incubation of PQ with plasmid DNA in the presence of freshly prepared rat lung microsomes and NADPH resulted in damage to the restriction site. The PQ-treated DNA was not digested with the endonuclease reflected by the digestion pattern of DNA on agarose gels. The effect was dependent on the dose of PQ. The PQ-mediated damage to DNA was comparable to DNA damage caused by ROS generated through the xanthine-xanthine oxidase system. The results of the present study suggest that ROS generated by PQ in vitro under aerobic conditions may lead to a modification of the restriction site on DNA.