Detection of 1,N2-Propanodeoxyguanosine Adducts as Potential Endogenous DNA Lesions in Rodent and Human Tissues

摘要: Our previous study (R.G. Nath and F-L. Chung; Proc. Natl. Acad. Sci. USA, 91: 7491-7495, 1994), using a 32P postlabeling method combined with high-performance liquid chromatography specifically developed for exocyclic adducts, has shown that acrolein- crotonaldehyde-derived 1,N2-propanodeoxyguanosine adducts (AdG CdG, respectively) are present in the liver DNA from humans rodents without carcinogen treatment. Those findings raised important questions regarding their role as potential endogenous lesions carcinogenesis. In this study, similar assay, we examined variety of tissues untreated rats mice (lung, kidney, brain, breast, prostate, colon, skin, leukocytes) detected AdG CdG these tissues. More significantly, also obtained evidence presence human leukocytes mammary glands. The identities were verified by comigration 3', 5' -bisphosphates 32P-labeled adduct synthetic standards reversed-phased chromatography. Additional proof was provided enzymatic conversion 3',5' to corresponding 5'-monophosphates, followed standards. estimated ranges total modifications various 0.10 1.60 mumol/mol guanine humans, based on recoveries external This demonstrated ubiquity tissues, suggesting endogeneous humans.