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© 1991 Oxford University Press

other

DNA methylation in specific cells of rat liver by N-nitrosodimethylamine and N-nitrosomethylbenzylamine

W.-D. Dai 2, V. Lee 1, W. Chin 1, D.P. Cooper, M.C. Archer and P.J. O'Connor

Cancer Research Camaign Section of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital and Holt Radium Institute Wilmslow Road, Manchester M20 9BX, UK
1Department of Medical Biophysics, University of Toronto, Ontario Cancer Institute 500 Sherbourne Street, Toronto M4X 1K9, Canada
2Present address: Department of Pharmacology and Medicine, Royal Hallampshire Hospital Sheffield S10 2JF, UK

Dose-response curves for the O6-methylation of guanine in the hepatic DNA of Wistar and Sprague-Dawley rats were determined after administration of N-nitrosomethylbenzyl-amine (NMBzA) or N-nitrosodimethylamine (NDMA). Similar results were obtained for both rat strains but methylation of hepatic DNA by NDMA was {small tilde}9-fold more efficient than with NMBzA when doses were compared on a molar basis. Comparison by immunohistochemical analysis of the distribution of nuclei containing O6-methylguanine within the liver lobules showed that both agents tended to alkylate cells close to the central veins at the lower doses. With increasing doses, the band width of alkylated cells around the central vein increased, spreading in the case of NDMA virtually into the portal zones, whereas with NMBzA the zone of alkylated nuclei reached little more than halfway from the central vein to the portal zone. These differences in the distribution of alkylated cells may explain the differing hepatic responses to these two nitrosamines.


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