Oxidative modification of DNA bases in rat liver and lung during chemical carcinogenesis and aging

Ying Jan Wang, Yuan Soon Ho, Ming Jiang Lo, Jen kun Lin

研究成果: Article同行評審

59 引文 斯高帕斯(Scopus)

摘要

The extent of DNA modification in cancerous rat liver and lung tissues was investigated and compared to their respective normal tissues. Liver tumors were induced by 2-fluorenyl-acetamide (2-FAA) or N-nitroso-N-2-fluorenylacetamide (N-NO-2-FAA), and lung tumors were induced by sodium nitrite plus trimethylamine. In the DNA samples isolated from these tissues, two pyrimidine-derived and four purine-derived modified DNA bases were identified and quantified by gas chromatography/mass spectrometry with selected-ion monitoring. These compounds were characterized as 5-hydroxyuracil (5-OHUra), thymine glycol (TG), 4,6-diamino-5-formamidopyrimidine (FapyAde), 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua), 8-hydroxyadenine (8-OHAde), and 8-hydroxyguanine (8-OHGua). Elevated amounts of modified DNA bases were found in most cancerous tissues when compared to the controls. Chemicals used for tumor induction were responsible for inducing DNA lesions that could be promutagenic in vivo and could lead to various types of mutations. When endogenous oxidative damage to DNA during aging was examined, a roughly 2-fold increase of thymine glycol, 8-OHAde and 8-OHGua was found in aged (12 months) rat liver tissues compared to young tissues (1 month). The same results were also found in lung tissues, except that the amount of thymine glycol exhibited more than a 10-fold increase in aged tissues when compared to young tissues. The association of the modified bases with the processes of aging and carcinogenesis deserves further investigation.

原文English
頁(從 - 到)135-145
頁數11
期刊Chemico-Biological Interactions
94
發行號2
DOIs
出版狀態Published - 1995 二月

All Science Journal Classification (ASJC) codes

  • 毒理學

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