Enitan A. Bababunmi

Some observations on the oxidation phenotype status of Nigerian patients presenting with cancer

The hypothesis is being explored that there may be an association between genetically determined oxidation status and propensity to develop carcinoma in response to environmental chemical carcinogens. For this purpose, the genetic structure of a normal, healthy Nigerian population with respect to oxidation status, has been compared with that found for a group of 59 Nigerian patients presenting with carcinoma of the liver and gastrointestinal tract. Genetically determined oxidation status was assessed by measuring the extent of oxidation of a probe drug, debrisoquine, to its major metabolite, 4-hydroxydebrisoquine. The cancer group contained a disproportionately large number of individuals who were extensive oxidizers compared to the controls (2 P = 0.0045). The findings support the view that genetically determined oxidation status may be an important host factor in influencing responsiveness to chemical carcinogens that require oxidative metabolic activation.

Comparison of the membrane-bound (Ca2++Mg2+)-ATPase in erythrocyte ghosts from some mammalian species

The properties of the membrane-bound calcium-pumping protein, the (Ca2+ + Mg2+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) were compared in erythrocyte ghosts isolated from five mammalian species--human (Homo sapiens), bovine (Bos taurus), porcine (Sus scrofa melitensis), ovine (Ovis aries crassicandus) and caprine (Capra hircus syriaca). The specific activity of the enzyme in porcine erythrocytes is one order of magnitude higher than in the other species. It was also stimulated to various extents by the regulator protein, calmodulin, and by phosphatidylinositol in all the species. Analysis of membrane proteins revealed a number of differences which seem to suggest that the molecular architecture of the red cell membrane influences the activity of the enzyme.

The uncoupling effect of N-(phosphonomethyl)glycine on isolated rat liver mitochondria.

Abstract The rates of oxygen consumption by rat liver mitochondria, respiring on either succinate, a two-site substrate, or β-hydroxybutyrate, a three-site substrate, and in the presence of varying concentrations of the isopropylamine salt of N -(phosphonomethyl) glycine (PMG) have been measured polarographically. The respiratory control ratios of these mitochondria were shown to be significantly reduced, by at least 10 per cent by the addition of 3.95 × 10 −5 M PMG. There was a larger decrease in these ratios, up to 50 per cent, as the concentration of the herbicide was raised to 1.25 × 10 −3 M. At concentrations ranging from 3.12 × 10 −4 M to 1.25 × 10 −3 M, PMG restored respiration of mitochondria previously inhibited by oligomycin. Adenosine triphosphatase (ATPase) activity was enhanced by the addition of PMG. In this respect, the maximal increase, 3-fold, was obtained at 6.25 × 10 −4 M PMG. These findings suggest that N -(phosphonomethyl) glycine uncouples oxidative phosphorylation in isolated rat liver mitochondria.

The presence of aflatoxin and some polycyclic aromatic hydrocarbons in human foods

An analysis of several common food items (fish, meat, crops and spices) as sold in the Nigerian markets has shown the presence of (a) benzo[a]-pyrene and benz[a]anthracene in fish and meat samples, and (b) aflatoxin in crops and spices. These results are discussed in relation to the relatively high incidence of cancer in tropical Africa.

Inhibition of succinate-linked reduction of pyridine nucleotide in rat liver mitochondria ‘in vivo’ by N-(phosphonomethyl)glycine

The pattern of the interaction of N-(phosphonomethyl)glycine (PMG), a broad-spectrum and non-selective herbicide with succinate-linked reduction of pyridine nucleotide, was investigated in liver mitochondria isolated 5 h after albino rats were given i.p. injections of PMG. Although there was no appreciable inhibition of the reduction of pyridine nucleotide at dosage levels less than 150 mg PMG/kg, the extent of inhibition increased as the dose was raised to 240 mg PMG/kg. Maximal inhibition of 34.5% and 45.4% were obtained at 240 mg PMG/kg when externally added ATP and high-energy intermediate, respectively, were used as the source of energy. These findings suggest that the inhibitory effect of PMG may be due to its uncoupling effect on oxidative phosphorylation.

Mutagenicity of chamuvaritin: A benzyldihydrochalcone isolated from a medicinal plant

The mutagenic effects of chamuvaritin, dihydrobenzylchalcone isolated from Uvaria chamae, were investigated using Salmonella typhimurium tester strains TA92, TA94--98, TA100--1535, TA1537 and TA1538. The phytochemical was mutagenic in tester strains TA98 and TA100 and required activation by the hepatic S-9 microsomal enzyme preparation.

Toxins and carcinogens in the environment: an observation in the tropics.

The incidence of primary liver cancer in the countries of tropical Africa is the highest in the world. There is a growing belief that the relatively high prevalence of hepatocellular carcinoma in Nigeria may have a multiple chemical factor etiology in such forms as food contaminants, herbal teas, and environmental chemicals. Major chemical toxins and carcinogens that have been identified so far in the tropical environment include sapotoxin, cycasin, mushroom toxin, capsaicin, oxalic acid, prussic acid, fluorooleic acid, N-nitroso compounds, aflatoxin, palmotoxin, pyrrolizidine alkaloids, quinine, DDT, and cyclamate.

Depression of the Ca2+-ATPase activity of the rat liver endoplasmic reticulum by the liver tumour promoters 1,1,1-trichloro-2,2-bis(p-chlorophenyl)- ethane and phenobarbital

The effects of a short-term in vivo administration of two liver tumour promoters (phenobarbital and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane on rat liver endoplasmic reticulum Ca(2+)-ATPase were investigated. The specific activity values of this membrane-bound enzyme significantly decreased (P less than 0.01) by 51% for phenobarbital-treated rats and by 48% for 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane-treated rats compared with control animals. The depression of liver endoplasmic reticulum Ca(2+)-ATPase appears to be a manifestation of the toxicological effect of tumour promoters.

Sickle-cell membrane-bound (Ca2+ + Mg2+)-ATPase: Activation by 3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-6-butyric acid, a novel antisickling agent

The effects of 3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-6-butyric acid (DBA), an antisickling agent, on the rates of Ca2+-dependent ATP hydrolysis by the human red cell (Ca2+ + Mg2+)-ATPase, have been studied in membranes (normal and sickle-cell) stripped of endogenous calmodulin. The activity of the enzyme is increased by DBA in a manner which is dependent on both the concentrations of DBA and Ca2+. At 37 degrees C, the normal red cell (Ca2+ + Mg2+)-ATPase activity is stimulated maximally by 133% in the presence of 1 mM DBA and 0.2 mM CaCl2, while the sickle-cell enzyme is stimulated maximally by 81% in the presence of 0.5 mM DBA and 0.2 mM CaCl2. The stimulation of the enzyme in both systems is antagonized by increasing the CaCl2 concentration in the medium to 0.5 mM, in contrast to the well established mode of activation by the modulator protein, calmodulin. This suggests that the two effectors, DBA and calmodulin, probably act by different mechanisms. From our present observations, we suggest that the antisickling effect of DBA may be connected with the mobilization of calcium within red cells.

The metabolic fate of [14C] benzoic acid in protein-energy deficient rats

The metabolic fate of [14C] benzoic acid administered i.p. to marasmic-kwashiorkor rats has been investigated. Rats fed a normal diet with benzoic acid administered i.p. at 200 mg/kg, excreted the benzoic acid mainly as hippuric acid (99% of 24 h excretion), while marasmic-kwashiorkor rats excreted 62--85% as hippuric acid and 14--37% as the glucuronide conjugate. 2 weeks after repletion metabolism of benzoic acid by the marasmic-kwashiorkor rats on the stock diet had returned to normal; most of the benzoate was excreted as hippuric acid.