The behaviour of nuclear proteins during nitrosamine-induced carcinogenesis.
Dimethylnitrosamine given after partial hepatectomy reduces the synthesis of DNA, histone, and, to a lesser extent, of nonhistone proteins, the inhibition being general rather than for specific nuclear proteins. The extent of inhibition of macromolecular synthesis is greatest when the carcinogen is given a few hours after the operation. As a higher incidence of hepatocellular carcinoma is induced when dimethylnitrosamine is injected later, during the wave of DNA replication, it appears that inhibition of nuclear protein synthesis is not a relevant factor in carcinogenesis, unless it relates to loss of a specific non-histone protein present in small amounts. Analysis of sequentially extracted groups of non-histone proteins by 2D electrophoresis did not reveal any changes produced by treatment with dimethylnitrosamine. Animals fed a diet containing diethylnitrosamine showed an increased incorporation of amino acid into histone. Electrophoretic analysis of non-histone proteins revealed two reproducible effects of feeding the carcinogenic diet: relative to the bulk of nuclear non-histone protein, there was a reduction in the amount of a slightly basic 65000 mol. wt. polypeptide, and an increase in the level of a high molecular weight protein that was almost undetectable in material from normal rats. As these changes were not induced by partial hepatectomy of normal animals, it is possible that they are related to malignancy rather than to the associated increase in cell replication.
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects; D004128:Dimethylnitrosamine / Q000633:toxicity*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006657:Histones / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008115:Liver Regeneration / Q000187:drug effects*; D009698:Nucleoproteins / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D006657:Histones; D009698:Nucleoproteins; D004128:Dimethylnitrosamine