This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Martelli, A. Articles by Brambilla, G. Search for Related Content PubMed PubMed Citation Articles by Martelli, A. Articles by Brambilla, G.

Comparative Study of DNA Damage and Repair Induced by Ten N-Nitroso Compounds in Primary Cultures of Human and Rat Hepatocytes¹

Institute of Pharmacology, University of Genoa [A. M., L. R., G. B.], and First Surgical Division of St. Martino Hospital [G. M. G.], 16132 Genoa, Italy

Ten carcinogenic N-nitroso compounds were assayed for DNA-damaging activity in primary cultures of human and rat hepatocytes. DNA fragmentation was measured by the alkaline elution technique, and unscheduled DNA synthesis by quantitative autoradiography. Positive dose-related responses in the range of subtoxic concentrations indicated were obtained in cells of both species with N-nitrosodiethylamine (10–32 mM), N-nitrosodi-n-propylamine (1.8–10 mM), N-nitrosomorpholine (1–3.2 mM), N-nitrosopiperidine (1–3.2 mM), N-nitrosopyrrolidine (3.2–18 mM), N-nitroso-N-methylurea (0.32–1.8 mM), N-nitroso-N-ethylurea (0.32–1.8 mM), and N-nitroso-N-butylurea (0.1–0.32 mM). N-nitrosodi-n-butylamine was practically inactive at the maximal soluble concentration (1 mM). The responses of human hepatocytes were qualitatively similar to those of rat hepatocytes, but statistically significant differences between the two species in the amounts of DNA damage and/or unscheduled DNA synthesis were observed with N-nitrosodimethylamine, N-nitrosomorpholine, N-nitrosopiperidine, N-nitrosopyrrolidine, and N-nitroso-N-butylurea. On the other hand, quantitative differences in the genotoxic effects induced by 5 mM N-nitrosodimethylamine in cultures derived from 20 human donors and from 20 rats were greater than average interspecies differences displayed by this nitrosamine and by other N-nitroso compounds. These results indicate that the rat hepatocyte DNA repair assay is a valid model for predicting the genotoxic potential of N-nitroso compounds in human hepatocytes.

¹ This work was supported by the Consiglio Nazionale delle Ricerche, Finalized Projects Oncology (contracts 86.00326.44 and 86.00470.44) and Preventive and Rehabilitative Medicine (contract 86.01877.56), and by funds of the Public Instruction Ministry.

² To whom requests for reprints should be addressed, at Istituto di Farmacologia dell'Università, Viale Benedetto XV, no. 2, I-16132 Genova, Italy.

Received 7/10/87. Revised 4/ 6/88. Accepted 4/ 8/88.

This article has been cited by other articles:

				J. F. Teiber and P. F. Hollenberg Identification of the human liver microsomal cytochrome P450s involved in the metabolism of N-nitrosodi-n-propylamine Carcinogenesis, August 1, 2000; 21(8): 1559 - 1566. [Abstract] [Full Text] [PDF]