Inhibition of 4-nitroquinoline 1-oxide induced unscheduled DNA synthesis in primary cultures of rat urothelial cells by dicumarol and pyrophosphate.
Primary cultures of rat urothelial cells were exposed to hydroxyurea, [3H]thymidine, and 4-nitroquinoline 1-oxide (NQO) or N-hydroxy-4-aminoquinoline 1-oxide (HAQO) in a serum-free media for 2 h; unscheduled DNA synthesis (UDS) was measured by autoradiography. Both NQO and HAQO produced unscheduled DNA synthesis. Dicumarol, an inhibitor of NQO nitroreductase, inhibited the activity of NQO and, to a lesser extent, HAQO. Pyrophosphate, an inhibitor of seryl-AMP synthetase, inhibited the activity of both compounds. Neither dicumarol nor pyrophosphate, under similar experimental conditions, inhibited the activity of N-hydroxy-N-2-acetylaminofluorene (N-OH-AAF). These results support the idea that nitro-reductase and seryl-AMP synthetase may be involved in the activation of NQO.
D015112:4-Nitroquinoline-1-oxide / Q000037:antagonists & inhibitors*; D000818:Animals; D001345:Autoradiography; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D001728:Dicumarol / Q000494:pharmacology*; D011756:Diphosphates / Q000494:pharmacology*; D005260:Female; D006881:Hydroxyacetylaminofluorene / Q000037:antagonists & inhibitors; D008297:Male; D009600:Nitroquinolines / Q000037:antagonists & inhibitors*; D051381:Rats; D001743:Urinary Bladder / Q000187:drug effects
D011756:Diphosphates; D009600:Nitroquinolines; D006881:Hydroxyacetylaminofluorene; D015112:4-Nitroquinoline-1-oxide; D001728:Dicumarol; D004247:DNA