DNA damage induced by seven N-nitroso compounds in primary cultures of human and rat kidney cells.
Seven N-nitroso compounds (NOC), known to induce kidney tumors in rats, were assayed for DNA-damaging activity in primary cultures of human and rat kidney cells. DNA fragmentation was measured by the alkaline elution technique. Positive responses were obtained in cells of both species with N-nitrosodimethylamine (32 mM), N-nitrosodiethylamine (32 mM), N-nitrosodi-n-propylamine (10 mM), N-ethyl-N-hydroxyethylnitrosamine (18 mM), and streptozotocin (1 mM). N-nitrosodiethanolamine and N-nitrosomorpholine were inactive at the highest concentration tested (32 mM). The responses of human kidney cells were qualitatively similar to those of rat kidney cells, but statistically significant differences between the two species in the DNA-damaging potencies were observed with N-ethyl-N-hydroxyethylnitrosamine and streptozotocin, both more genotoxic in rat cells. Taken as a whole, the results suggest on the one hand that the five active NOC might be carcinogenic for the kidney in humans, and on the other hand that the rat kidney cell/DNA damage assay is a valid model for predicting the genotoxic potential of NOC in human kidney cells.
Robbiano
L
L
Institute of Pharmacology, University of Genoa, Italy.
Mereto
E
E
Corbu
C
C
Brambilla
G
G
D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000493:pharmacokinetics / Q000633:toxicity*; D002478:Cells, Cultured; D004249:DNA Damage; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects*; D008297:Male; D009603:Nitroso Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D009603:Nitroso Compounds