Formation of M1G-dR from endogenous and exogenous ROS-inducing chemicals.
The present study provides fundamental information regarding the production of M1G-dR by ROS. To investigate the production of M1G-dR from deoxyribose damage as caused by ROS, calf thymus DNA (CT-DNA) was incubated with NAD(P)H, CuCl2, and various concentrations of hydrogen peroxide (H2O2). The incubation of CT-DNA with H2O2 resulted in concentration-dependent increases in the number of M1G-dR adducts. In subsequent experiments, 1,4-tetrachlorobenzoquinone or catechol estrogens were evaluated for their effects on M1G-dR formation. In addition, the role of lipid peroxidation in the formation of M1G-dR was verified using an in vitro lipid peroxidation model which consisted of methyl esters of either fish oil or purified fatty acids found in cellular membranes. This experiment confirmed that M1G-dR is a major DNA adduct produced by lipid peroxidation. Furthermore, the number of double bonds in polyunsaturated fatty acids was found to be the key factor in the formation of M1G-dR. The findings obtained from this study provide important information regarding the molecular pathways for M1G-dR formation by ROS, which is an essential element in understanding and evaluating the genotoxicity of a variety of ROS-inducing chemicals.
Jeong
Yo-Chan
YC
Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Swenberg
James A
JA
D004247:DNA / Q000737:chemistry; D018736:DNA Adducts / Q000096:biosynthesis* / Q000737:chemistry; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry; D003855:Deoxyribose / Q000737:chemistry; D002393:Estrogens, Catechol / Q000737:chemistry; D005227:Fatty Acids / Q000737:chemistry; D005395:Fish Oils / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000737:chemistry; D015227:Lipid Peroxidation; D008738:Methyl Ethers / Q000737:chemistry; D009249:NADP / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism*
D018736:DNA Adducts; D002393:Estrogens, Catechol; D005227:Fatty Acids; D005395:Fish Oils; D008738:Methyl Ethers; D017382:Reactive Oxygen Species; D009249:NADP; D003855:Deoxyribose; C089188:3-(2'-deoxyribofuranosyl)pyrimido(1,2-a)purin-10(3H)-one; D004247:DNA; C427203:calf thymus DNA; D006861:Hydrogen Peroxide; D003849:Deoxyguanosine