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Changes in de Novo DNA (Cytosine-5-)-methyltransferase Activity in Oncogenically Susceptible Rat Target Tissues Induced by N-Methyl-N-nitrosourea¹

Institut de Biologie Moléculaire et Cellulaire du CNRS et Faculté de Pharmacie, Université Louis Pasteur, 15 rue Descartes, 67084 Strasbourg, France

The activity of de novo DNA (cytosine-5-)-methyltransferase (DNA methylase) in various rat tissues after administration of a single dose of N-methyl-N-nitrosourea (MNU) has been analyzed. The total and specific activities of the DNA methylase of the brain, where tumor induction is important, are increased. In kidney, the DNA methylase activity first increases up to 16 h and decreases afterwards. Liver DNA methylase activity does not change. This organ is not susceptible to MNU induced cancers. Because organs in which the DNA methylase activity is high or increased after MNU are more prone to carcinogenesis by this compound, we argue that there is a relationship between the effects of MNU and DNA methylase activity.

¹ This work was partly supported by Institut National de la Santé et de la Recherche Médicale (INSERM, Contrat 85/2009) and the Ligue Nationale Française contre le Cancer, Comité Départemental du Haut-Rhin.

Received 3/ 4/85. Revised 7/24/85. Revised 10/18/85. Accepted 11/14/85.