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THE addition of copper salts to a diet containing a carcinogenic azo dye affords a degree of protection against hepatocarcinogenesis to rats consuming the diet (Howell, 1958). It has also been found that rats which are fed 3'-methyl-4-dimethylaminoazobenzene (Neish, 1959b) or which receive single intraperitoneal injections of various hepatocarcinogens (Neish, 1958(Neish, , 1959a) suffer a marked decline in the serum levels of total copper and of the copper-containing enzyme para-phenylenediamine oxidase (caeruloplasmin). The degree and persistence of this decline appear to be correlated closely with the carcinogenic potency of the injected materials. These results suggest that a derangement of copper metabolism in rat livers may occur at an early stage in hepatocarcinogenesis.Serum levels of total copper and caeruloplasmin are generally subnormal in patients with hepatolenticular degeneration (Scheinberg and Sternlieb, 1959) and Uzman (1957) and Uzman et al. (1956) have detected an abnormal copper-avid ninhydrin-reacting substance, possibly a peptide, in the livers of such patients. It seemed important to determine whether hepatocarcinogens could induce the formation of similar abnormal peptides in rat liver. Although work on this aspect is not yet complete it has been found that injection of hepatocarcinogens into rats increases the levels of certain ninhydrin-positive materials in the liver.Firstly, it was established qualitatively by paper chromatographic and electrophoretic investigations of phosphate or ethanol extracts of rat liver that intraperitoneal injections of hepatocarcinogens caused a marked increase in the level of "free " phosphoethanolamine (PE) in this tissue. In general, a strong hepatocarcinogenii evoked and maintained a higher level of PE for a longer time than did a weaker one.Secondly, it was found that the livers of rats injected with hepatocarcinogens contained one or two unidentified ninhydrin-positive substances X and Y which migrated towards the anode during paper electrophoresis at pH 8.6. Spot X was observed regularly after the application of a strong hepatocarcinogen and its intensity seemed to run parallel with the intensity of PE. Y was not always present when X occurred but it often appeared when X was rather intense. Traces of X but not of Y have been noted occasionally in extracts of normal rat liver. The nature of X and Y has not yet been completely elucidated but there is evidence that these substances are acidic peptides and that X at least seems to be closely related to glutathione.In the present paper we shall discuss in detail the effect of hepatocarcinogens onI the content of free PE in rat livers. In a future publication the occurrence and nature of the peptide-like materials X and Y will be considered in relation to similar substances which have been found in the livers of tumour-bearing rats and in tumour extracts.

Rapid separation of synthetic mixtures of the 2,4‐dinitrophenylhydrazone derivatives of α‐keto acids has been effected by paper electrophoresis. The method has been applied to the separation of these derivatives from animal tissues and a polarographic procedure has been devised for the estimation of the hydrazones. Keto acid analyses are presented for organs from normal and tumour‐bearing rats.