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Metabolism of Low Concentrations of N-Nitrosodimethylamine in Isolated Liver Cells of the Guinea Pig¹

Institute of Toxicology, University of Tübingen, Wilhelmstrasse 56, D 7400 Tübingen [G. H., H. R., M. S.], and Chemische Landesuntersuchungsanstalt, Breitscheidstrasse 4, D 7000 Stuttgart [R. F.], Federal Republic of Germany

Freshly isolated liver cells of guinea pig were used to study the metabolism of NDMA in the concentration range 0.05 to 100 µM. Analysis was performed using the gas chromatograph-thermal energy analyzer nitrosamine detector method and with radiolabeled NDMA. At concentrations below 10 µM, NDMA was degraded by liver cells (10 mg of protein in 2.5 ml of medium) within 20 min (at 100 µM in 80 min). The majority of metabolized methyl groups were initially associated with volatile compounds and were subsequently integrated into nonvolatile, acid-soluble molecules (57%) or liberated as CO₂ (14%). Less than 2% were bound to cellular macromolecules. Ethanol inhibited NDMA degradation competitively, with a K_i of 0.8 mM ethanol. It is concluded that low concentrations of NDMA are metabolized in liver cells, primarily by the high-affinity demethylase and that there are no additional catalytic activities with K_m values below 5 µM. Most of the methyl groups, released during metabolism, enter the C₁ pool.

¹ Supported by the Deutsche Forschungsgemeinschaft.

² To whom requests for reprints should be addressed.

Received 8/23/83. Accepted 12/16/83.