Gabriel Hocman

Chemoprevention of cancer: Phenolic antioxidants (BHT, BHA)

1. The synthetic phenolic antioxidants (e.g. BHT, BHA) added to human and animal food are able to lengthen the life of organisms and lower the incidence of cancer caused by chemical compounds. 2. On the other hand they may not be rendered completely harmless since they can cause lung damage (BHT) or promote the action of some carcinogens (BHA). 3. They could act as compounds preventing cancer either via interception of harmful free radicals, activating the detoxifying enzymes of the body, inhibiting the formation of ultimately carcinogenic metabolites and their binding to DNA, and modifying the immune response of the organism. 4. Their action is influenced by their own chemical structure, the composition of carcinogen, the strain, sex and age of experimental animals, the tissue upon which they are supposed to act and the time of their administration in relation to the time of the carcinogen insult. 5. These compounds are concentrated in adipose tissue, liver and kidney. They are excreted within tens of hours mainly in urine. 6. The acceptable daily intake of BHA is at present considered to be 0.6 mg kg-1 body wt day-1. In spite of their possible tumor-promoting properties they could not be considered overtly toxic. Their pronounced chemoprotective role against some forms of chemical carcinogenesis deserves considerable attention.

Chemoprevention of cancer: Selenium

1. Selenium intake (in the form of selenite, selenate, selenomethionine, etc.) protects the organism against the action of some kinds of carcinogens. 2. People and animals having less Se in their blood are at a higher risk of acquiring cancer than those whose blood contains more of this element. 3. This chemopreventive action is probably due to antioxidant properties of Se, its involvements in the enzyme glutathione peroxidase as well as in the inhibition of enzymes converting carcinogens to their ultimate forms in the cell. 4. An intake of 150-300 micrograms of Se daily is considered to be adequate to protect the human organism without exhibiting the toxic properties of this element.

Chemoprevention of cancer: protease inhibitors

1. The defense of the organism against cancer by inhibitors of proteolytic enzymes which are able to block the metastasizing stage of the disease is reviewed. 2. The contemporary views on the possible mechanisms of the process of prevention on both molecular and cellular levels are presented.

Biochemistry of ageing.

Abstract The experimental and theoretical papers concerning ageing on the molecular and cellular level published mainly in 1977 are critically reviewed. The main accent is placed upon the introduction of new ideas and hypotheses.

Cetaben is an exceptional type of peroxisome proliferator.

1. Cetaben in contrast to fibrates affect differently peroxisomal constituents. 2. Changes in large scale of liver non-peroxisomal parameters were compared after 10 days administration of equal doses (200 mg/kg/day) of cetaben and clofibric acid to male Wistar rats. 3. Clofibric acid treatment increased markedly the activities of FAD-glycerol-3-P dehydrogenase, beta-hydroxyacyl-CoA dehydrogenase, cytochrome-c oxidase, malic enzyme, NAD-glycerol-3-P dehydrogenase, ethoxycoumarin deethylase, p-nitroanisole demethylase and amounts of cytochrome P-450 and b5. 4. However no analogical changes were observed after cetaben treatment in the livers of experimental animals. 5. Both drugs increased the activities of alanine-glyoxylate aminotransferase-1 and acetylcarnitine transferase--enzymes with proven mitochondrial and peroxisomal location. 6. Cetaben contrary to clofibric acid does not increase solubilization of peroxisomal enzymes. 7. Enhanced acetylcarnitine transferase and alanine-glyoxylate aminotransferase-1 activities were distributed in mitochondria as well as in peroxisomes after clofibric acid treatment, however, only peroxisomes were enriched after cetaben administration. 8. The results obtained suggest that cetaben represents an exceptional type of peroxisome proliferator, specifically affecting peroxisomes, without having a negative influence on the processes of peroxisome biogenesis.

Biochemistry of ageing and cancer

Abstract Recent (1977–1979) results and ideas concerning both ageing and cancerogenesis are critically reviewed from the point of view of molecular events as well as those on the cellular level.

The use of Sephadex in the chromatography of thyroxine-containing compounds: a critique.

Abstract A critical assessment is made of the separation of thyroxine, free and bound to plasma proteins, and of iodide by means of gel filtration on Sephadex. The following sources of error are discussed: (I) Spontaneous degradation of thyroxine to iodide. (2) The effect of the shape and size of the column on the relative proportions of the separated substances. (3) The effect of the adsorption of free thyroxine on the Sephadex material. The ways by which thyroxine is eluted from the column are also discussed and the error for the method is determined.

Human thyroxine-binding globulin. Isolation and chemical properties. II. Properties.

Abstract 1. 1. The physical and chemical properties of human blood thyroxine binding globulin (TBG) isolated by different authors are summarized and compared. 2. 2. The relative contribution of some of the characteristic groups of the thyroxine molecule to its binding to TBG is discussed.

Cetaben and fibrates both influence the activities of peroxisomal enzymes in different ways

The effects of cetaben and clofibric acid were compared on the activities of peroxisomal enzymes in the liver and kidney of male Wistar rats. Cetaben at 200 mg/kg body wt increased the activities of all of the enzymes in the liver that were studied two to eight times, whereas the changes induced by the same dose of clofibric acid increased some of the enzymes and decreased others. In the kidney, cetaben increased the activities of all investigated peroxisomal enzymes, while clofibric acid only increased the activity of palmitoyl-CoA oxidase. The data obtained in the dose-response study of cetaben revealed a significant rise in the activities of peroxisomal enzymes in both the liver and kidney at doses of 50-100 mg/kg body wt administered over 10 days, but the maximal effect was observed at 250 mg/kg. Palmitoyl-CoA oxidase and D-amino acid oxidase respond most markedly to cetaben. Cetaben could represent an atypical peroxisomal proliferator, since it increased the activities of all peroxisomal enzymes investigated. The fact that the individual components localized in the peroxisomes do not change markedly could be of importance with respect to the function and physical properties of peroxisomes.

Gel filtration of thyroxine-binding proteins: group separation of soluble proteins of rat liver on sephadex gels

Abstract 1. 1. The separation of radiothyroxine-labelled proteins of rat liver homogenate by gel filtration on Sephadex G-150 shows four radioactive peaks: A, a fraction containing the bulk of proteins present; B, a fraction containing most of the specific thyroxinc-bmding proteins, with specific radioactivity about six times greater than that of the first peak; C, radioiodide; D, residual free radiothyroxinc, adsorbed to the column. 2. 2. The separation of Sephadex G-200 showed three distinct fractions, two of them con-taining the specific thyroxine-binding proteins, the third one containing the bulk of high molecular weight, non-binding proteins.