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Effects of Carcinogenic Amines on Amino Acid Incorporation by Liver Systems

II. A Morphological and Biochemical Study on the Effect of Dimethylnitrosamine^*

Tapen Mukherjee, Rune G. Gustafsson, Björn A. Afzelius and Erik Arrhenius

( Department of Biophysics and Department of Cell Physiology, The Wenner-Gren Institute for Experimental Biology, University of Stockholm, Stockholm, Sweden)

Comparative morphological and biochemical studies have been performed on liver from rats treated in vivo with dimethylnitrosamine (DMN) in doses ranging from 20 to 100 mg/kg body wt. and in a time range of 2–20 hours. A reduced capacity of mitochondria-free liver homogenates to incorporate labeled amino acids into proteins was confirmed with short-time in vivo treatments (2–3 hours). Electron microscopy on liver tissue from the same animals revealed marked changes in the endoplasmic reticulum but no notable effects on other cellular structures.

Prolongation of in vivo treatment to 20 hours enhanced the inhibitory effect in the high dose range (100 mg/kg body wt.). The morphological investigation of the liver from these animals revealed generalized damage of the liver cytoplasm and indications of necrobiosis.

After 20 hours' treatment in vivo with a low dose (20 mg/kg body wt.), on the other hand, a stimulation of the amino acid incorporation activity in cell-free systems was obtained, which masked the primary inhibition. The stimulatory effect was associated with an increase in the glycogen content. The structural changes, which have been considered to be reflected in this secondary stimulation of microsomal functions, were a marked swelling of the rough-surfaced endoplasmic reticulum, and great amounts of glycogen clusters appearing in the regions of the enlarged smooth endoplasmic reticulum. The secondary stimulation is interpreted as being mainly due to an increased sensitivity of the liver to glucocorticoids.

^* This work was supported by research grants from the U.S. Public Health Service (C-5278) and the Swedish Cancer Society. One of the authors (T. M.) was a fellow at the Central Committee for Swedish Technical Assistance and acknowledges the Council of Scientific and Industrial Research, Government of India, for allowing leave of absence.

Present address: Chittaranjan National Cancer Research Centre, 37 S.P. Mookerjee Road, Calcutta, India.

Received 2/12/63.