Blood of patients with gastric tumor was studied after their admission to the hospital and alter the chemotherapeutic course. Formation of the tumor was accompanied by development of hypovitaminoses B-1 and PP. The vitamin deficiency was more distinct after treatment of the patients with cylophosphan: content of thiamine diphosphate (TDP), was decreased by 40 %; NAD+NADP, by 30 % and NADH+ +NADPH, by 20 %. In mice with Ehrlich ascites carcinoma, activity of transketolase in erythrocytes was decreased by 48 %, content of TDP, by 61 % and that of NADPH, by 27 %. The administration of cyclophosphan increased further thiamine deficiency in the tumor-bearing mice. Simultaneous administration of thiamine and cyclophosphan abolished the cytostatic toxic effect but did not affect their antitumoral properties. Under these conditions treatment with vitamins B-1 and PP complex was undesirable due to malignization. The vitamins B-1 and PP did not stimulate the tumor growth, partially restored impaired metabolism of the vitamins and may be included separately into combined multidrug oncotherapeutics.

The daily intragastric administration of 25% ethanol solution during 14 days resulted in an increase of the NAD liver concentration by 15%. The supplementary administration of riboflavin and pantothenate increased to a greater extent the hepatocyte level of NAD. The exogenous administration of vitamin PP normalized NAD and NADP in the liver of all alcohol-treated animals.

Oxythiamine injections to rats (400 mg/kg of body mass, subcutaneously, 2 injections with 48 hrs interval) caused 70% involution of thymus within 72 hrs after the first injection. The transketolase activity was inhibited by 70%, that of glucose-6-phosphate dehydrogenase by 15%, while the aldopentose level was decreased by 56% in the thymus. Inhibition of DNA and RNA synthesis was directly dependent on the dose and duration of the oxythiamine effect on the gland. Reduction of transketolase activity was accompanied by an adaptive; increase in glucose-6-phosphate dehydrogenase activity as well as by a decrease in levels of nicotinamide coenzymes (NAD, NADP) in spleen.

Turnover of [14C]thiamin was studied in mice with Ehrlich ascites carcinoma fed a thiamin-deficient diet and injected with 5 or 2 micrograms/mouse of the labeled vitamin. The process of conversion of [14C]thiamin to thiamin pyrophosphate (TPP) was monitored by measuring the activities of transketolase, pyruvate dehydrogenase, and oxoglutarate dehydrogenase. The amount of coenzyme-unsaturated apotransketolase was assessed by measuring the TPP effect--determining transketolase activity with and without the addition of TPP in vitro. Tumor growth was accompanied by thiamin deficiency, manifested in an increase in [14C]thiamin incorporation into the host tissues and the absence of saturation of the tissues with the labeled vitamin over 13 days. Increased values for the turnover coefficients, reduction of thiamin-dependent enzyme activities, elevation of the TPP effect, and a decrease in urinary excretion of the radioactive products also provided evidence for a disturbance in thiamin metabolism. The severity of the disturbance in thiamin metabolism during malignant tumor growth was directly related to the dose of the exogenous vitamin.

A study was made of turnover of [14C]thiamin (5 or 2 micrograms/mouse) in mice fed a thiamin-deficient diet. Simultaneously the activities of the thiamin-dependent enzymes (transketolase, pyruvate and oxoglutarate dehydrogenases) were measured as an index of efficiency of fulfilling the coenzyme function of the vitamin under conditions of different thiamin status. After [14C]thiamin injections of 5 micrograms/mouse, kidney, spleen, stomach and pancreas tissue stores turned over completely on day 9, whereas by day 13 this process had not yet been finished in liver, heart and brain. On administration of 2 micrograms [14C]thiamin/mouse, turnover of the tissue stores proceeded at a slower rate. The tissue transketolase activity decreased after the 2-microgram injections as compared to that in the mice administered 5-microgram injections. With 2 micrograms of [14C]thiamin, the pyruvate dehydrogenase activity lowered gradually in all the tissues studied, whereas the oxoglutarate dehydrogenase decreased in liver and kidneys. The pattern of the depression of the thiamin-dependent enzyme activities after the 2-microgram [14C]thiamin injections suggests a regularity in the vitamin redistribution in different organs and subcellular fractions.

Thiamine pyrophosphate (TPP) content, activities of thiamine pyrophosphokinase (TPKase), thiamine pyrophosphatase, transketolase (TK), pyruvate (PDG) and oxoglutarate dehydrogenases (OGDG) were measured in the liver and cells of Ehrlich ascites carcinoma (EAC) on the 5th, 10th and 15th day after transplantation of the tumor to mice fed a thiamine-deficient diet. The TPP level gradually decreased in the liver of tumor-bearing mice but remained constant in tumor cells (1.06 +/- 0.02 microgram/g tissue). Deprivation of dietary thiamine lowered the liver TPP level even to a greater extent, and subsequent daily 10 micrograms thiamine/mouse injections did not restore it. The TPKase activity in the liver of mice with EAC decreased by 24% and in thiamine deficiency, by 44%. The liver PDG, OGDG and TK activities were reduced but slightly in mice with EAC, whereas thiamine deprivation resulted in a decrease of the enzyme activities: PDG by 60%, OGDG by 25% and TK by 45%. TK activity in tumor cells was 90 mumol S-7-P/g tissue/h, and the TPP effect amounted to 24%. Thiamine deprivation decreased the TK activity by 45% and raised the TPP effect up to 180%. Thiamine injections restored the TK activity in tumor cells and reduced the TPP effect.