Korean J Urol.
1993 Feb;34(1):16-25.
Formation of 8-hydroxydeoxyguanine moiety in human bladder cellular DNA by bladder carcinogens
- Affiliations
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- 1Department of Urology, Seoul National University, College of Medicine, Seoul Korea.
- 2Department of Phamacology, Seoul National University, College of Medicine, Seoul Korea.
Abstract
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The 8-hydroxydeoxyguanosine (8-OH-dG), DNA adduct produced by oxygen radical-induced hydroxylation of C-8 position of guanine residue is accepted as to cause mutation and associate with carcinogenesis, and there are many carcinogens those produce oxygen radicals. Although many carcinogens have been accepted to induce bladder tumor, there is little known about the mechanism of carcinogenesis by these carcinogens. Following administration of bladder carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), 4-Aminobiphenyl (4-ABP), 2-naphthylamine (2-NA) and N-methyl-N-nitrosourea (MNU) to human normal bladder epithelial cell, the results were obtained.1. Following administration of aromatic amine carcinogen, BBN, 4-ABP and 2-NA, the content of 8-OH-dG was increased to about 30-35 % although some variation of time existed according to the kinds of carcinogens. 2. Following administration of MNU, the content of 8-OH-dG was increased to about less than 3 % over all times. 3. Following administration of H2O2 that produce oxygen radicals without metabolism, the content of 8-OH-dG was increased to about 37 %. From this result, it can be supposed that the in crease of 8-OH-dG by carcinogens is induced by oxygen radical.The results obtained suggest that there are some enzymes in bladder epithelium that are related to metabolism of aromatic amine carcinogens and modification of DNA in bladder epithelial cell by the oxygen radicals, that is Formation of 8-OH-dG, is induced in carcinogenesis of bladder tumor byaromatic amine carcinogens.