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J D Groopman

Publications and source records attributed to J D Groopman.

At least 91 records · Page 5Linked to original sources
PubMed1992

Molecular dosimetry of urinary aflatoxin-DNA adducts in people living in Guangxi Autonomous Region, People's Republic of China.

Hepatocellular carcinoma is one of the five leading human cancers causing at least 250,000 deaths each year. One of the major risk factors for this disease is exposure to dietary aflatoxins, and the development of appropriate molecular dosimetry biomarkers would facilitate the identification of individuals at risk. This study was undertaken to explore the relationship between dietary intake of aflatoxins and the excretion of the major aflatoxin-DNA adduct and other metabolites into the urine of chronically exposed people. The following protocol was developed for this investigation in Guangxi Autonomous Region, People's Republic of China, where the diets of 30 males and 12 females (ages, 25-64 years) were monitored for 1 week and aflatoxin intake levels determined each day. Starting on the fourth day, total urine volumes were obtained in consecutive 12-h fractions for 3 or 4 days. High performance liquid chromatography and competitive radioimmunoassay analyses were done on each of the urine samples, and the relationships between excretion of total aflatoxin metabolites, aflatoxin-N7-guanine, aflatoxin M1, aflatoxin P1, and aflatoxin B1, and aflatoxin B1 intake values were determined. The average intake of aflatoxin B1 by men was 48.4 micrograms/day, giving a total mean exposure during the study period of 276.8 micrograms. The average daily intake by women was 77.4 micrograms/day, resulting in a total average exposure during the 7-day period of 542.6 micrograms aflatoxin B1. Initial efforts to characterize aflatoxin metabolites in urine samples were with an analysis by competitive radioimmunoassay. The analysis by linear regression of the association between aflatoxin B1 intake/day and total aflatoxin metabolite excretion/day showed a correlation coefficient of only 0.26. These findings stimulated the immunoaffinity/analytical high performance liquid chromatography analysis for individual metabolites. When the data were analyzed by linear regression analysis, the aflatoxin N7-guanine excretion and aflatoxin B1 intake from the previous day showed a correlation coefficient of 0.65 and P less than 0.000001. Similar analysis for aflatoxin M1 resulted in a correlation coefficient of 0.55 and P less than 0.00001, whereas there was no positive statistical association between exposure in the diet and aflatoxin P1 excretion, despite aflatoxin P1 being quantitatively a major metabolite. Analysis of the total aflatoxin-N7-guanine excretion in the urine during the complete collection period plotted against the total aflatoxin B1 exposure in the diet for each of the individuals, smoothing the day to day variations, revealed a correlation coefficient of 0.80 and P less than 0.0000001.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Aflatoxins isolated by immunoaffinity chromatography from foods consumed in The Gambia, West Africa.

An aflatoxin-specific, monoclonal antibody-based immunoaffinity chromatography method has been developed for the rapid isolation of aflatoxins from human foods. Aflatoxins were isolated by immunoaffinity chromatography from a variety of cooked foods, including maize, rice, millets, groundnut sauces, and leaf sauces, collected in The Gambia, West Africa. The aflatoxins were measured by direct fluorescence or high-pressure liquid chromatography. The highest levels were found for groundnut sauces, mean 162 ppb (range 18 to 943 ppb) for 18 positive samples, but aflatoxins were found in other foods; e.g., maize, mean 9.7 ppb (range 2 to 35 ppb) for nine positive samples. The food analysis results were used with records of the amounts of cooked food to estimate a mean daily intake for an individual of the order of 3.5 micrograms of aflatoxins per day. This approach for exposure assessment is considered in relation to other biomarkers of aflatoxin exposure using biological fluids.

Aflatoxins↗
PubMed1992

Molecular dosimetry of urinary aflatoxin-N7-guanine and serum aflatoxin-albumin adducts predicts chemoprotection by 1,2-dithiole-3-thione in rats.

Hepatocellular carcinoma has one of the poorest 5 year survival rates of any human cancer. Preventive measures offer the best possibility of ameliorating this disease and chemoprotective agents are being developed for this purpose. The dithiolethiones, including oltipraz and the unsubstituted molecule 1,2-dithiole-3-thione, have been shown to be potent inhibitors of aflatoxin-induced hepatic tumorigenesis in rats. However, subsequent evaluation of dithiolethiones or other chemoprotective agents in human clinical trials will require the development of intermediate, non-invasive biomarkers to evaluate the efficacy of these interventions. In this study, levels of molecular dosimetry biomarkers for determining genotoxic damage caused by aflatoxin B1 have been measured in a chronic exposure model with male F344 rats wherein half the animals were fed a diet supplemented with 0.03% 1,2-dithiole-3-thione to lower their risk for tumors and the other half were fed unsupplemented AIN-76A diet and were at high risk for tumor development. Levels of hepatic aflatoxin-DNA adducts, serum aflatoxin-albumin adducts and excreted aflatoxin-N7-guanine adducts in urine were determined following multiple administrations of 250 micrograms aflatoxin B1/kg body wt on days 0-4 and 7-11 to assess the use of the serum and urinary biomarkers as indices of chemoprotective efficacy. In the rats fed 1,2-dithiole-3-thione, the overall diminutions in the levels of hepatic DNA adducts, urinary aflatoxin-N7-guanine and serum aflatoxin-albumin adducts over the 2 week exposure period were 76, 62 and 66% respectively. This parallelism in reductions of levels of biomarkers relative to target organ DNA adduct burden suggests that these biomarkers are predictive short-term, non-invasive measures for assessing the efficacy of chemoprotective interventions in experimental studies and can be applied to human clinical trials directed at populations at high risk for aflatoxin exposure and primary hepatocellular carcinoma.

Aflatoxin B1↗
PubMed1992

Potent inhibition of aflatoxin-induced hepatic tumorigenesis by the monofunctional enzyme inducer 1,2-dithiole-3-thione.

1,2-Dithiole-3-thiones are five-membered cyclic sulfur-containing compounds with antioxidant, chemotherapeutic, radioprotective and chemoprotective properties. Several substituted 1,2-dithiole-3-thiones are used medicinally and one of these, oltipraz [5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione], has been recently shown to be an inhibitor of aflatoxin B1 (AFB1) hepatocarcinogenesis in the rat. Structure-activity studies have been undertaken to probe the mechanisms by which dithiolethiones inhibit carcinogenesis. Such studies revealed that unsubstituted 1,2-dithiole-3-thione was more effective than oltipraz at inhibiting aflatoxin-DNA adduct formation in vivo and at inducing electrophile detoxication enzymes in cell culture. In the present studies the effects of dietary administration of 1,2-dithiole-3-thione on the induction of xenobiotic metabolizing enzymes and inhibition of aflatoxin-induced hepatic tumorigenesis were examined. Male F344 rats were fed graded doses of 1,2-dithiole-3-thione (0.001-0.03%) for 4 weeks. During the second and third weeks of 1,2-dithiole-3-thione feeding, rats were dosed by gavage with 250 micrograms of AFB1/kg five times a week. Rats were then restored to control AIN-76A diet 1 week after cessation of AFB1 dosing. At 4 months, focal areas of hepatocellular alteration were identified and quantified by staining sections of liver for gamma-glutamyltranspeptidase (GGT) activity and glutathione S-transferase P (GST-P) expression. Treatment with 1,2-dithiole-3-thione at the lowest dose (0.001%) reduced by greater than 80% the volume of liver occupied by GGT or GST-P foci; higher dietary concentrations provided greater than 98% reductions in the volume per cent of these markers for presumptive preneoplastic lesions. All dietary concentrations of 1,2-dithiole-3-thione resulted in significant elevations in hepatic GST activities. In accord with the protective effects against tumorigenesis, 4- to 6-fold increases in the specific activities of aflatoxin-glutathione conjugation were observed in cytosols prepared from livers of animals fed 1,2-dithiole-3-thione. By contrast, 1,2-dithiole-3-thione did not have any detectable inductive effects on hepatic microsomal cytochrome P450 levels or activities. Dietary administration of 1,2-dithiole-3-thione also elevated activities of GSTs and other phase II enzymes in several extrahepatic organs. This broad pattern of induction of detoxication enzymes by 1,2-dithiole-3-thione supports the potential widespread use of this compound as a protective agent against chemical carcinogenesis and other forms of electrophile toxicity.

Aflatoxin B1↗
PubMed1992

Aflatoxin M1 in human breast milk from The Gambia, west Africa, quantified by combined monoclonal antibody immunoaffinity chromatography and HPLC.

Maternal to child exposure of aflatoxin M1 in breast milk is an underevaluated risk factor from dietary exposure to aflatoxin B1. A molecular dosimetry study in The Gambia, West Africa, was initiated to explore the relationships between dietary intake of aflatoxins during a 1 week period and a number of aflatoxin biomarkers including aflatoxin metabolite excretion into breast milk. For the breast milk study, five lactating women were identified and milk samples were collected by hand expression once a day during days 3-7 for three women and during days 3-6 for the two other women. Aflatoxin M1 (AFM1) in human milk was measured in all five subjects by a preparative monoclonal antibody immunoaffinity column/HPLC method. In three of the five women, aflatoxin G1 was found. Estimates of the percentage of aflatoxin in the diet excreted as AFM1 in milk ranged from 0.09 to 0.43%. Thus, these data indicate that a rapid methodology exists to assess the levels of AFM1 excretion in human milk and to use this approach as a biomarker for exposure of children to this carcinogen.

Aflatoxin M1↗
PubMed1992

Aflatoxin B1--DNA adduct formation in rat liver following exposure by aerosol inhalation.

There is growing concern that human exposure to respirable grain dust contaminated with aflatoxin B1 (AFB1), a potent hepatocarcinogen, may be a risk factor for a number of human diseases. The objective of this study was to determine if liver DNA adduct formation occurs in rats following either intratracheal injection or nose-only aerosol inhalation exposure to AFB1. Male Fischer 344 rats were exposed by both routes of administration, and in preliminary data using intratracheal instillation, up to 2% of the administered dose became bound to liver DNA. In the nose-only aerosol inhalation experiments, rats were exposed for up to 120 min. Immediately after exposure, four animals were killed at each time point and their livers removed, DNA isolated and purified and analyzed for aflatoxin-DNA adducts by HPLC. A linear dose-response relationship was observed with a correlation coefficient of 0.96 between increasing length of exposure, and the amount of aflatoxin-N7-guanine adducts formed per mg DNA, the mean values and standard errors were 4.2 +/- 0.18, 15.3 +/- 4.3, 21.6 +/- 2.8 and 56.8 +/- 4.6 pmol aflatoxin-DNA adducts per mg DNA for the 20, 40, 60 and 120 min exposures respectively. The amounts of aflatoxin-DNA adducts formed were statistically significantly different (P less than 0.01) among the treated groups. These results indicate that aerosol inhalation is an effective route of exposure to AFB1 in rats that results in genotoxic damage in the liver.

Administration, Inhalation↗
PubMed1992

Monoclonal antibodies and rabbit antisera recognizing 4-aminobiphenyl--DNA adducts and application to immunoaffinity chromatography.

Monoclonal antibodies and rabbit antisera were produced that recognized 4-aminobiphenyl, its major DNA adducts and other metabolites. The antigens used to raise these antibodies were synthesized by coupling the aromatic amine to protein through a diazotization reaction. The goal of this immunization strategy was to induce antibodies that also cross-reacted with most 4-aminobiphenyl-derived metabolites. A total of 20 mice and four rabbits were immunized and every animal produced a strong immune response for 4-aminobiphenyl and its derivatives. Two IgG1 monoclonal antibodies, 3D6 and 2E11, were isolated from two different mouse spleen cell fusions. One of the monoclonal antibodies, 3D6, had a high recognition for the three major 4-aminobiphenyl-DNA adducts: N-(deoxyguanosine-8-yl)-4-aminobiphenyl, N-(deoxyadenosin-8-yl)-4-aminobiphenyl and N-(deoxyguanosine-N2-yl)-4-aminobiphenyl, with affinity constants between 2 and 4 x 10(9) l/mol. In addition, one of the rabbit anti-sera had an affinity constant for the DNA adducts of 2.1 x 10(9) l/mole. Thus, the strategy to use a diazotization coupling reaction was successful at producing high-affinity aminobiphenyl-DNA adduct-specific antibodies. Preparative immunoaffinity resins were made for each monoclonal antibody. These resins quantitatively bound 500 ng each [3H]N-acetyl-aminobiphenyl, [3H]N-aminobiphenyl and [3H]N-(deoxyguanosine-8-yl)-4-aminobiphenyl. Preliminary experiments were performed to test the applicability of the preparative monoclonal antibody immunoaffinity column to isolate [3H]4-aminobiphenyl-derived metabolites in dosed rat and dog urine. About 70% of the radioactivity in rat or dog urine could be bound to the immunoaffinity columns. The combined immunoaffinity column/HPLC analysis of the dog urine led to the identification of a novel urinary metabolite, N-formyl-aminobiphenyl. HPLC analysis of a rat urine sample tentatively found 4-aminobiphenyl, N-acetyl-4-aminobiphenyl and N-formyl-4-aminobiphenyl by co-chromatography, and these compounds accounted for 20, 6.8 and 6.5% of the total radioactivity in the chromatogram respectively. Taken together, these data show that these 4-aminobiphenyl-specific monoclonal antibodies can be used in immunoaffinity columns to isolate metabolites and DNA adducts from biological samples.

Aminobiphenyl Compounds↗
PubMed1992

Elucidation of catalytic specificities of human cytochrome P450 and glutathione S-transferase enzymes and relevance to molecular epidemiology.

A number of different approaches have been used to determine the catalytic selectivity of individual human enzymes toward procarcinogens. Studies with cytochrome P450 (P450) enzymes and glutathione S-transferases are summarized here, and recent work with pyrrolizidine alkaloids, aflatoxins, 4,4'-methylenebis(2-chloroaniline), and ethyl carbamate is discussed. In some cases a single enzyme can catalyze both activation and detoxication reactions of a chemical. The purification and characterization of human lung P4501A1 and the development of a noninvasive assay for human P4502E1 are also described.

Aflatoxin B1↗
PubMed1992

Molecular dosimetry of aflatoxin DNA adducts in humans and experimental rat models.

Primary hepatocellular carcinoma is one of the most common and lethal cancers in the world. It is particularly prevalent on the continents of Africa and Asia. A number of epidemiological studies have associated the exposure status of people to aflatoxin B1 as being important in the etiology of liver cancer. However, to date these studies have relied upon the criteria of presumptive intake data, rather than relying upon quantitative analyses of aflatoxin DNA adduct and metabolite content obtained by monitoring biological fluids from exposed people. Information obtained by monitoring exposed individuals for specific DNA adducts and metabolites will define the pharmacokinetics of aflatoxin B1 in people, thereby facilitating risk assessments. In combination with the human monitoring studies is the need to use animals models to help provide an interpretable data base for the human results. Animal models are also going to be critical to the development of chemoprotection strategies. The molecular dosimetry studies described in this chapter support the concept that measurement of the major, rapidly excised AFB-N7-guanine adduct in urine is an appropriate dosimeter for estimating exposure status and possibly risk in individuals consuming this mycotoxin.

Aflatoxins↗
PubMed1991

Protection against aflatoxin B1-induced hepatocarcinogenesis in F344 rats by 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione (oltipraz): predictive role for short-term molecular dosimetry.

Previous studies have demonstrated that dietary administration of the schistosomicidal drug 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione (oltipraz) ameliorates the hepatotoxicity of aflatoxin B1 (AFB1). Notably, mortality, altered hepatic function, hepatic AFB1-DNA adduct levels, and expression of hepatic enzyme-altered foci were markedly reduced in the rat by concurrent feeding of oltipraz during exposures to AFB1. Collectively, these studies prompted us to evaluate the chemoprotective properties of oltipraz against AFB1-induced liver cancer. In addition, preliminary molecular dosimetry studies were undertaken to determine the utility of measurements of urinary aflatoxin-N7-guanine excretion as a marker of relative risk for hepatocarcinogenesis in AFB1-exposed rats. For the carcinogenesis studies, 5-wk-old male F344 rats were randomly divided into two groups. One group (55 rats) received the AIN-76A diet, and the other group (56 rats) received the AIN-76A diet supplemented with 0.075% oltipraz. The oltipraz-supplemented diet was fed for 4 wk. Beginning 1 wk after starting the experimental diets, all rats in both groups received 25 micrograms of AFB1/rat/day by gavage for 5 days per wk over the next 2 wk. One wk following cessation of dosing with AFB1, oltipraz was removed from the diet, and all rats were fed the AIN-76A diet for the remainder of the experiment. At 3 mo after dosing, livers of ten sentinel rats from each group were analyzed for the burden of gamma-glutamyltranspeptidase-positive foci. In accord with previous findings, rats fed the oltipraz-supplemented diet exhibited substantial reductions in the focal burden (97% reduction; P less than 0.05) of these AFB1-induced lesions. The remaining rats were maintained for the cancer study until they became moribund or the termination of the experiment at 23 mo. Gross liver lesions were identified at autopsy and confirmed by microscopic evaluation. An 11% incidence of hepatocellular carcinoma was observed in the AFB1-treated, control diet-fed rats. An additional 9% of this group had hepatocellular adenomas. Oltipraz afforded complete protection against both AFB1-induced hepatocellular neoplasms. Using Kaplan-Meier survival analyses, rats in the oltipraz group had a significantly (P less than 0.02) longer life span and an increased survival free of liver tumors (P less than 0.0002). Molecular dosimetry studies used rats fed either the oltipraz-supplemented or control diet for 1 wk and then challenged with a single dose of AFB1 to examine the initial rates of 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 excreted in the urine.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoma↗
PubMed1990

Aflatoxin-DNA adduct formation in chronically dosed rats fed a choline-deficient diet.

Nutritional modulation of male Fischer rats by a choline-deficient/methionine-low diet dramatically increases hepatocarcinogenesis and reduces time to first tumors induced by aflatoxin B1 (AFB1). The effect of this diet on hepatic aflatoxin-DNA adduct burden in male Fischer rats dosed with a carcinogenic regimen of AFB1 was examined in this study. After 3 weeks of ingestion of a choline-deficient/methionine-low diet or control semi-purified diet, rats were administered a carcinogenic regimen of 25 micrograms [3H]AFB1 for 5 days a week over 2 weeks. Six choline-deficient and four control diet rats were killed 2 h after each dose, and liver DNA isolated. In addition, hepatic DNA was isolated from animals 1, 2, 3, and 11 days after the last [3H]AFB1 administration. At all time points HPLC analysis of aflatoxin-DNA adducts was performed to confirm radiometric determinations of DNA binding levels. No significant quantitative differences in AFB1-DNA adduct formation between the dietary groups were observed following the first exposure to [3H]AFB1; however, total aflatoxin-DNA adduct levels in the choline-deficient animals were significantly increased during the multiple dose schedule. When total aflatoxin-DNA adduct levels were integrated over the 10 day dose period, a 41% increase in adduct burden was determined for the choline-deficient animals. While this increase in DNA damage is consistent with the hypothesis that DNA damage is related to tumor outcome, the biochemical basis for this effect still needs to be elucidated.

Aflatoxin B1↗
PubMed1990

The aflatoxin-lysine adduct quantified by high-performance liquid chromatography from human serum albumin samples.

Aflatoxin B1 (AFB1) exposure from the diet is a major risk factor for the development of liver cancer in people living in regions of China and Africa. Rapid methods to assess the exposure status of these individuals to genotoxic damage imparted by AFB1 will be very important for cancer prevention strategies. Serum albumin is a readily accessible target protein for AFB1 and we report here the development of an accurate and sensitive method to quantitate the major AFB1 serum albumin adduct, aflatoxin-lysine, from less than 100 microliters of serum by combined immunoaffinity chromatography/high-performance liquid chromatography (IAC/HPLC) with fluorescence detection. For this method, serum is digested with Pronase and the adducts are purified by monoclonal antibody IAC and quantified by HPLC. Analysis of human serum samples obtained from an exposed population revealed a highly significant correlation coefficient (up to 0.82 for male samples) between aflatoxin-lysine adduct levels and AFB1 consumption. These data suggest that aflatoxin-lysine is an excellent molecular dosimeter for exposure assessment. To determine whether the liver is the sole site of aflatoxin-albumin adduct formation, preliminary experiments with isolated perfused rat liver were done. These data showed that AFB1 metabolites covalently react not only with albumin in the hepatocyte, but also with circulating proteins in the perfusate. This suggests that a reactive aflatoxin metabolite secreted by the liver may form serum albumin adducts in circulating blood. Taken together, the analysis of aflatoxin-lysine could prove a very useful tool for epidemiological studies.

Aflatoxin B1↗
PubMed1990

Distribution of aflatoxins in tissues of growing pigs fed an aflatoxin-contaminated diet amended with a high affinity aluminosilicate sorbent.

The effect of hydrated sodium calcium aluminosilicate (HSCAS) added to the diet of swine fed an aflatoxin-contaminated diet on tissue aflatoxin levels was investigated. Pigs were fed control (less than 10 ng/g B1 + B2), contaminated (500-600 ng/g B1 + B2), and contaminated +0.5% HSCAS diets. Tissues analyzed for the presence of aflatoxin B1, B2, and M1 residues included liver, muscle, kidney, and adipose. Addition of HSCAS to the contaminated diet significantly reduced the amount of M1 in liver, kidney, and muscle tissue. Aflatoxin B1 was not reduced in liver or kidney, but was decreased in muscle.

Aflatoxins↗
PubMed1989

Antibody-antigen binding in organic solvents.

We describe, for the first time, the action of antibodies in anhydrous organic solvents. It has been demonstrated that the binding of a hapten, 4-aminobiphenyl, to the immobilized monoclonal antibody 2E11 is strong and specific not only in water but also in a variety of non-aqueous media. Further, the strength of interaction between antibody and hapten has been related to the hydrophobicity of the solvent: the more hydrophobic the solvent, the weaker the protein-ligand interaction.

Aminobiphenyl Compounds↗
PubMed1988

Immunochemical quantitation of DNA adducts derived from the human bladder carcinogen 4-aminobiphenyl.

To assess target-tissue exposure to the human urinary bladder carcinogen 4-aminobiphenyl (ABP), we have developed a sensitive immunochemical method for measuring the major arylamine-DNA adduct formed, N-(guan-8-yl)-ABP (Gua-C8-ABP). High-affinity polyclonal antisera from rabbits immunized with N-(guanosin-8-yl)-ABP coupled to keyhole limpet hemocyanin were characterized and shown to have high specificity for antigenic determinants on the purine and biphenyl rings of Gua-C8-ABP and minimal cross-reactivity with ABP, deoxyguanosine, or hydrolyzed DNA. Assay standards containing ABP-modified DNA were prepared by reacting [3H]N-hydroxy-ABP with calf thymus DNA. DNA samples were hydrolyzed with trifluoroacetic acid and dried under vacuum, and the residues were dissolved in dimethyl sulfoxide under argon. Using a streptavidin-biotin amplified enzyme-linked immunosorbent assay, DNA hydrolysates competed at 25 micrograms DNA/microtiter well for a limiting amount of anti-keyhole limpet hemocyanin-(Gua-C8-ABP) in the presence of excess solid-phase bovine serum albumin-(Gua-C8-ABP) coating antigen. The limit of sensitivity for this assay using 25 micrograms DNA was 2 adducts/10(8) nucleotides. Gua-C8-ABP adducts in liver and bladder epithelial DNAs were readily quantified after p.o. administration of 5 mg/kg ABP to dogs. This methodology is capable of detecting adducts at levels of biological significance and should be applicable to human target-tissue dosimetry.

Aminobiphenyl Compounds↗
PubMed1988

Protection by 5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz) against the hepatotoxicity of aflatoxin B1 in the rat.

A new chemoprotective agent, oltipraz, was evaluated for alleviation of aflatoxin B1-induced hepatotoxicity. Male F344 rats were fed a diet supplemented with 0.075% oltipraz and compared to rats fed the purified diet (AIN) alone. Rats were fed these diets for 1 week prior to treatment with aflatoxin B1 (AFB1) and throughout the experimental period. AFB1 was administered to rats by gavage in single doses ranging from 0.25 to 10 mg/kg body weight for acute toxicity studies and in multiple doses of 0.25 mg/kg, 5 days/week, for 2 weeks for subchronic toxicity studies. The latter protocol constitutes a tumorigenic dosing regimen. In an acute toxicity study, pretreatment with oltipraz reduced from 83 to 36% the mortality produced by 10 mg/kg AFB1. Oltipraz significantly suppressed the elevated serum levels of alanine amino transaminase and sorbitol dehydrogenase induced by sublethal doses of AFB1. In subchronic toxicity studies, the AFB1-treated rats fed AIN diet failed to gain weight over the 2-week treatment period and their liver weights were severely depressed. In contrast, the rats fed the oltipraz supplemented diet maintained a high rate of growth during AFB1 treatment. The subchronic AFB1 treatment regimen also resulted in over 75% loss of prelabeled [3H]thymidine from the liver while oltipraz supplementation largely prevented this loss. Taken together, these results indicate that oltipraz is very effective in ameliorating the toxic effects of AFB1 in rats.

Aflatoxin B1↗
PubMed1988

Serum albumin adducts in the molecular epidemiology of aflatoxin carcinogenesis: correlation with aflatoxin B1 intake and urinary excretion of aflatoxin M1.

Aflatoxin-serum albumin adducts in the blood of 42 residents of Guangxi Province, People's Republic of China, were determined and compared with intake of aflatoxin B1 (AFB1) and excretion of aflatoxin M1 (AFM1) in urine. Blood specimens were obtained during the same period that urine was collected and that diet was sampled. Serum albumin was isolated from blood by affinity chromatography on Reactive Blue 2-Sepharose and subjected to enzymatic proteolysis using Pronase. Immunoreactive products were purified by immunoaffinity chromatography and quantified by competitive radioimmunoassay. A highly significant correlation (r = 0.60, P less than 0.00003) of adduct level with AFM1 excretion was observed. An equally highly significant correlation of adduct level with intake (r = 0.69, P less than 0.000001) was also observed. From the slope of the regression line for adduct level as a function of intake, it was calculated that 1.4-2.3% of ingested AFB1 becomes covalently bound to serum albumin, a value very similar to that observed when rats are administered AFB1.

Aflatoxin B1↗