Induction of DNA Repair Synthesis in Human Urothelial Cells by the N-Hydroxy Metabolites of Carcinogenic Arylamines234
- 1 April 1984
- journal article
- research article
- Published by Oxford University Press (OUP) in JNCI Journal of the National Cancer Institute
- Vol. 72 (4), 847-852
- https://doi.org/10.1093/jnci/72.4.847
Abstract
Urinary N-hydroxy metabolites of carcinogenic arylamines were investigated for their abilities to induce unscheduled DNA synthesis (UDS) in human urothelial cell lines HCV 29, HU 1734, and HU 1752, and in a primary culture of human urothelial cells. N-Hydroxy-2-aminofluorene (CAS: 53-94-1; N-OH-AF), N-hydroxy-2-acetylaminofluorene (CAS: 53-95-2; N-OH-AAF), and the N-glucuronide of N-OH-AF induced UDS in HCV 29, HU 1734, and HU 1752. N-Hydroxy-4-aminobiphenyl (CAS: 6810-26-0; N-OH-ABP), N-hydroxy-4-acetylaminobiphenyl (CAS: 4463-22-3; N-OH-AABP), N-hydroxy-2-aminonaphthalene (CAS: 613-47-8; N-OH-AN), N-hydroxy-2-acetylaminonaphthalene (CAS: 2508-23-8; N-OH-AAN), and the N-glucuronide of N-OH-ABP induced UDS in HCV 29. However, the N-glucuronide of N-OH-AN did not. The O-glucuronide of N-OH-AAF induced UDS in HCV 29 only when β-glucuronidase was present. Paraoxon inhibited the induction of UDS in HCV 29 by N-OH-AAF and N-acetoxy-2-acetylaminofluorene (CAS: 6098-44-8), but not by N-OH-AF. When examined in a primary culture of human urothelial cells, N-OH-AF, N-OH-AAF, N-OH-ABP, and N-OH-AABP were active, but N-OH-AN, N-OH-AAN, 2-aminonaphthalene (CAS: 91-59-8), 2-aminofluorene (CAS: 153-78-6;), and 4-aminobiphenyl (CAS: 92-67-1) were not. These results demonstrate that human urothelial cells are able to activate both acetylated and non-acetylated N-hydroxy metabolites of carcinogenic arylamines, and they suggest that O-glucuronidation may be a detoxification mechanism for N-arylacethydroxamic acids.Keywords
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