Changes in Function and Structure of the Endoplasmic Reticulum of Rat Liver Cells after Administration of Cysteine

During experiments on the counteraction of the toxic effects of the carcinogen dimethylnitrosa-mine (1, 2) by cysteine (3, 4), it appeared that sub-cutaneous administration of 150 mg cysteine twice daily during 2 days to adult rats (inbred strain R-Amsterdam) led to a marked increase in the amount of material present in the liver microsomal fraction. The present paper briefly describes some of the biochemical and morphological observations pertaining to this finding of which a more comprehensive account will be given later. All experiments were performed on the day following 2 consecutive days of cysteine administration. As a result of the latter treatment the biochemical composition of the liver was markedly altered. The RNA, 1 protein, and PL-P contents of the liver microsomal fraction (per unit volume of a suspension of the 105,000 g pellet prepared from a 9000 or 12,000 g supernatant) were increased by about 30 to 50, 35 to 70, and 25 to 50 per cent, respectively. The relative increase in the protein content of the microsomes isolated from cysteine-treated livers was consistently found to be much higher than that of the nuclear and mitochondrial fractions, which, in general, showed little change. An increase of 20 to 50 per cent in the soluble protein was also noted. The liver glycogen dropped to 60 to 90 per cent of the normal content. However, neither the concentration of s-RNA nor that of endogenous leucine present in the soluble fraction changed as a result of the cysteine treatment. Per unit amount of fresh liver weight, the D N A increased by 20 per cent; it remains to be de-a Abbreviations used: RNP = ribonucleoprotein; ER = endoplasrnic reticulum; RNA = ribonucleic acid; s-RNA = soluble RNA; PL-P = phospholipid phosphor; MAB = 4-monomethylaminoazoben-zene; DPNH and TPNH = reduced di-and triphos-phopyridine nucleotides. cided whether this was due to cell shrinkage or to an increased D N A content per cell. The water content of the cysteine-treated livers was not decreased , but in most cases the liver weight (per 100 grams of body weight) was increased as compared with that of normal rats. Incubation of the postmitochondrial fractions (9000 or 12,000 g supernatants, consisting of microsomes plus cell sap (5)) from normal and cysteine-treated livers with leucine-l-C 14 showed a higher incorporation of label into the proteins of the latter than of the former preparations, the counts/min/mg protein being 1.5 to 2.5 …