Purine degradative enzymes and terminal transferase in acute myelogenous leukemia: clinical relevance.

Intracellular adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and terminal deoxynucleotidyl transferase (TdT) activities were investigated in adult patients with acute myelogenous leukemia (AML) in order to relate these enzymatic activities to the stage of differentiation and maturation and to the clinical outcome of AML. Both ADA and PNP were measured spectrophotometrically using the method of Hopkinson et al., and TdT was investigated using liquid scintillation technique with slight modification. The level of ADA was above normal in patients with AML whereas the level of PNP and the PNP/ADA ratio were below normal. Short survival was observed in the majority of the patients with markedly increased levels of ADA and decreased levels of PNP and PNP/ADA. Normal patients and patients with AML had no significant differences in TdT activity. Significant differences in ADA, PNP and TdT among AML subtypes were not observed. The levels of ADA and PNP seemed to reflect the clinical severity of this disease.

First clinical experiences with a selective chemotherapy of hepatocellular carcinoma with 5-fluorouridine in combination with other antipyrimidines.

Sixteen unselected patients with non-resectable hepatocellular carcinoma were treated in a phase I study with 261 cycles of D-galactosamine and 6-azauridine prior to 5-fluorouridine. Thirty % of the patients survived for more than one year without signs of tumor progression and with an unchanged performance status. The compatibility of this chemotherapeutical method was quite satisfactory. The only extrahepatic side effect was a leucopenia and/or thrombocytopenia which was reversible upon reduction of the 5-fluorouridine dose. The heterogeneity of the 16 patients treated to date does not allow a definite statistical evaluation of the reported clinical observations and results. A final decision about the clinical applicability of this concept of a selective chemotherapy of hepatocellular carcinoma requires further experience.

High-performance liquid chromatography of aflatoxins in human urine.

A method was developed for the extraction and determination of unconjugated aflatoxins in human urine by high-performance liquid chromatography. The analysis is based on the elimination of lipid-soluble constituents other than unconjugated aflatoxins in urine by light petroleum extraction. The unconjugated aflatoxins were subsequently extracted from the aqueous phase with chloroform-acetone. Chromatography was performed isocratically with a silica column at 40 degrees C. The resolved aflatoxins were detected and identified by ultraviolet and fluorometric detectors. The recoveries of aflatoxins B1 and G1 added prior to the extraction were 72% and 83%, respectively. This procedure is simple, sensitive and practically useful for epidemiological survey of unconjugated aflatoxins in human urine from areas with a high risk of aflatoxin consumption.

Influence of dietary protein and vitamin B12 on the toxicity and carcinogenicity of aflatoxins in rat liver.

The influence of dietary protein content and dietary vitamin B12 supplement on the hepatotoxicity and carcinogenicity of aflatoxin in rat liver was studied. In animals fed a low-protein diet, aflatoxin induced extensive toxic and carcinogenic effects. Cirrhosis was significantly prevented to a certain level by vitamin B12 administration, but the incidence of cholangiofibrosis and hyperplastic nodules was unchanged. No toxic effect was observed in animals receiving high-protein diet with no vitamin B12 supplement in this study (33 weeks). Only one rat bearing a hepatoma was observed in this group. However, hepatoma and hyperplastic nodules were found in the group receiving high-protein diet plus vitamin B12. Cholangiofibrosis and cirrhosis were not observed in the high-protein group regardless of vitamin B12 administration.