The initiative of the Organisation for Economic Co-operation and Development (OECD) to establish ... more The initiative of the Organisation for Economic Co-operation and Development (OECD) to establish biological resources centres (BRCs) and eventually a Global Biological Resources Centres Network (GBRCN) is a welcome one at a time when loss of biodiversity is becoming a critical concern to scientists and many governments.
The effects of primaquine treatment on antioxidant enzyme activities were investigated in rat liv... more The effects of primaquine treatment on antioxidant enzyme activities were investigated in rat liver and kidney. Male Sprague-Dawley rats were treated with 0.21 mg/kg daily for two weeks (chronic treatment) or a single dose at 0.21 or 0.63 mg/kg. Antioxidant enzyme activities were determined in liver and kidney cytosolic fractions whereas glutathione (GSH) and malondialdehyde (MDA) levels were determined in tissue samples. Results for the liver showed increases in cytosolic superoxide dismutase (SOD) and glutathione peroxidase (GPX) enzymatic activities after chronic primaquine treatment. Levels of MDA, a marker for lipid peroxidation, were also increased by more than 50% indicating enhanced oxidative damage in the liver. In the single dose study, 0.63 mg/kg primaquine caused a more than 100% increase in liver SOD and a 36% increase in NAD (P) H: quinone oxidoreductase (NQOR) activities. Results for the kidney, however, showed fewer primaquine-induced changes in antioxidant enzyme activities when compared to the liver in both the chronic and single dose studies. Overall, our results indicate that primaquine treatment causes an oxidative stress in the two rat organs. These results are consistent with the known pro-oxidant effects of primaquine in vivo, and supplement current knowledge on the effects of antimalarial drugs on various enzyme systems.
The objective of this study was to determine the CYP2D6 genotype of a black Zimbabwean population... more The objective of this study was to determine the CYP2D6 genotype of a black Zimbabwean population. Genotyping was carried out using Eco RI and Xba I RFLP, and allele-specific PCR amplification. Of 114 Zimbabwean samples analysed, no individual homozygous for any of the defect allelic forms CYP2D6A, CYP2D6B or CYP2D6D or combinations thereof was found. The allele frequencies of the three defect genes were 0, 1.8 and 3.9%, respectively. No subject carrying the Xba I 44 kb haplotype, indicative for poor metabolizers among Caucasians, was identified, whereas five individuals being heterozygous with a 29/42 kb haplotype were seen. Three out of the four CYP2D6B alleles found were associated with the 29/42 kb haplotype. Our findings are in agreement with the 0-2% prevalence of poor metabolizers (PMs) in the black populations previously phenotyped. The very low frequency of the CYP2D6B allele in the Zimbabwean population is different from very recent data from black Americans (allele frequency = 8.5%) and might indicate the Caucasian ancestry of this allele. Taken together, our data indicate important interethnic differences in the CYP2D locus between Caucasian, Asian and different black populations.
The development of molecular dosimetry methods will simplify the identification of people at high... more The development of molecular dosimetry methods will simplify the identification of people at high risk for cancer. A combined monoclonal antibody ¡mmunoaffinity chromatography/high performance liquid chro- matography method has been devised to isolate and quantify aflatoxin- DNA adducts and other metabolites in rat urine samples. We report the production of 11 different monoclonal antibodies recognizing aflatoxin B,, aflatoxin <.),. aflatoxin
Clinical chemistry and laboratory medicine : CCLM / FESCC, 2004
Cytochrome P450 1A2 (CYP1A2) is an important member of the cytochrome P450 superfamily of enzymes... more Cytochrome P450 1A2 (CYP1A2) is an important member of the cytochrome P450 superfamily of enzymes because of its involvement in the metabolism of some carcinogens and therapeutically important drugs. As a result, factors affecting the activity of the enzyme are the focus of considerable research effort as they may have important pharmacological or toxicological implications. CYP1A2 has been shown to exhibit a genetic polymorphism with most of the data, however, coming from studies in Caucasian and Oriental populations. In this study therefore, we investigated the frequencies of two point mutations, -163C>A and 63C>G, in two Bantu African populations. A total of 214 healthy subjects were recruited from Zimbabwe (n=143) and Tanzania (n=71). The two single nucleotide polymorphisms were detected using polymerase chain reaction-restriction fragment length polymorphism analysis. The frequency of -163A was 57% (95% confidence interval (CI), 54%, 60%) and 49% (95% CI, 45%, 53%) among ...
Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology, 1990
1. In a previous study of the marine sponge Geodia mesotriaena von Lendenfeld for antineoplastic ... more 1. In a previous study of the marine sponge Geodia mesotriaena von Lendenfeld for antineoplastic constituents, evidence was obtained for the presence of several toxins and geodiatoxin 1 was isolated. 2. Further separations guided by bioassay using CDF1 mice have led to the isolation of three additional chromoprotein toxins lethal at 8 mg/kg.
The development of molecular dosimetry methods will simplify the identification of people at high... more The development of molecular dosimetry methods will simplify the identification of people at high risk for cancer. A combined monoclonal antibody immunoaffinity chromatography/high performance liquid chromatography method has been devised to isolate and quantify aflatoxin-DNA adducts and other metabolites in rat urine samples. We report the production of 11 different monoclonal antibodies recognizing aflatoxin B1, aflatoxin Q1, aflatoxin G1, aflatoxicol, and aflatoxin M1 and the application of these antibodies to a multiple monoclonal antibody affinity chromatography technique. Using the multiple monoclonal antibody affinity column with rat urines obtained from dosed animals, between 90 and 95% of total aflatoxin metabolites can be bound to the column and isolated. Analytical immunoaffinity chromatography/high performance liquid chromatography analysis of these isolated aflatoxins reveals that more than 55% of the aflatoxins in rat urine are aflatoxin-dihydrodiol, aflatoxin-N7-guani...
The initiative of the Organisation for Economic Co-operation and Development (OECD) to establish ... more The initiative of the Organisation for Economic Co-operation and Development (OECD) to establish biological resources centres (BRCs) and eventually a Global Biological Resources Centres Network (GBRCN) is a welcome one at a time when loss of biodiversity is becoming a critical concern to scientists and many governments.
The effects of primaquine treatment on antioxidant enzyme activities were investigated in rat liv... more The effects of primaquine treatment on antioxidant enzyme activities were investigated in rat liver and kidney. Male Sprague-Dawley rats were treated with 0.21 mg/kg daily for two weeks (chronic treatment) or a single dose at 0.21 or 0.63 mg/kg. Antioxidant enzyme activities were determined in liver and kidney cytosolic fractions whereas glutathione (GSH) and malondialdehyde (MDA) levels were determined in tissue samples. Results for the liver showed increases in cytosolic superoxide dismutase (SOD) and glutathione peroxidase (GPX) enzymatic activities after chronic primaquine treatment. Levels of MDA, a marker for lipid peroxidation, were also increased by more than 50% indicating enhanced oxidative damage in the liver. In the single dose study, 0.63 mg/kg primaquine caused a more than 100% increase in liver SOD and a 36% increase in NAD (P) H: quinone oxidoreductase (NQOR) activities. Results for the kidney, however, showed fewer primaquine-induced changes in antioxidant enzyme activities when compared to the liver in both the chronic and single dose studies. Overall, our results indicate that primaquine treatment causes an oxidative stress in the two rat organs. These results are consistent with the known pro-oxidant effects of primaquine in vivo, and supplement current knowledge on the effects of antimalarial drugs on various enzyme systems.
The objective of this study was to determine the CYP2D6 genotype of a black Zimbabwean population... more The objective of this study was to determine the CYP2D6 genotype of a black Zimbabwean population. Genotyping was carried out using Eco RI and Xba I RFLP, and allele-specific PCR amplification. Of 114 Zimbabwean samples analysed, no individual homozygous for any of the defect allelic forms CYP2D6A, CYP2D6B or CYP2D6D or combinations thereof was found. The allele frequencies of the three defect genes were 0, 1.8 and 3.9%, respectively. No subject carrying the Xba I 44 kb haplotype, indicative for poor metabolizers among Caucasians, was identified, whereas five individuals being heterozygous with a 29/42 kb haplotype were seen. Three out of the four CYP2D6B alleles found were associated with the 29/42 kb haplotype. Our findings are in agreement with the 0-2% prevalence of poor metabolizers (PMs) in the black populations previously phenotyped. The very low frequency of the CYP2D6B allele in the Zimbabwean population is different from very recent data from black Americans (allele frequency = 8.5%) and might indicate the Caucasian ancestry of this allele. Taken together, our data indicate important interethnic differences in the CYP2D locus between Caucasian, Asian and different black populations.
The development of molecular dosimetry methods will simplify the identification of people at high... more The development of molecular dosimetry methods will simplify the identification of people at high risk for cancer. A combined monoclonal antibody ¡mmunoaffinity chromatography/high performance liquid chro- matography method has been devised to isolate and quantify aflatoxin- DNA adducts and other metabolites in rat urine samples. We report the production of 11 different monoclonal antibodies recognizing aflatoxin B,, aflatoxin <.),. aflatoxin
Clinical chemistry and laboratory medicine : CCLM / FESCC, 2004
Cytochrome P450 1A2 (CYP1A2) is an important member of the cytochrome P450 superfamily of enzymes... more Cytochrome P450 1A2 (CYP1A2) is an important member of the cytochrome P450 superfamily of enzymes because of its involvement in the metabolism of some carcinogens and therapeutically important drugs. As a result, factors affecting the activity of the enzyme are the focus of considerable research effort as they may have important pharmacological or toxicological implications. CYP1A2 has been shown to exhibit a genetic polymorphism with most of the data, however, coming from studies in Caucasian and Oriental populations. In this study therefore, we investigated the frequencies of two point mutations, -163C>A and 63C>G, in two Bantu African populations. A total of 214 healthy subjects were recruited from Zimbabwe (n=143) and Tanzania (n=71). The two single nucleotide polymorphisms were detected using polymerase chain reaction-restriction fragment length polymorphism analysis. The frequency of -163A was 57% (95% confidence interval (CI), 54%, 60%) and 49% (95% CI, 45%, 53%) among ...
Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology, 1990
1. In a previous study of the marine sponge Geodia mesotriaena von Lendenfeld for antineoplastic ... more 1. In a previous study of the marine sponge Geodia mesotriaena von Lendenfeld for antineoplastic constituents, evidence was obtained for the presence of several toxins and geodiatoxin 1 was isolated. 2. Further separations guided by bioassay using CDF1 mice have led to the isolation of three additional chromoprotein toxins lethal at 8 mg/kg.
The development of molecular dosimetry methods will simplify the identification of people at high... more The development of molecular dosimetry methods will simplify the identification of people at high risk for cancer. A combined monoclonal antibody immunoaffinity chromatography/high performance liquid chromatography method has been devised to isolate and quantify aflatoxin-DNA adducts and other metabolites in rat urine samples. We report the production of 11 different monoclonal antibodies recognizing aflatoxin B1, aflatoxin Q1, aflatoxin G1, aflatoxicol, and aflatoxin M1 and the application of these antibodies to a multiple monoclonal antibody affinity chromatography technique. Using the multiple monoclonal antibody affinity column with rat urines obtained from dosed animals, between 90 and 95% of total aflatoxin metabolites can be bound to the column and isolated. Analytical immunoaffinity chromatography/high performance liquid chromatography analysis of these isolated aflatoxins reveals that more than 55% of the aflatoxins in rat urine are aflatoxin-dihydrodiol, aflatoxin-N7-guani...
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