SEARCH · PubMed Health

Results for “Aflatoxin”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 307 records · Page 17Linked to original sources

PubMed1999

Protective alterations in phase 1 and 2 metabolism of aflatoxin B1 by oltipraz in residents of Qidong, People's Republic of China.

BACKGROUND: Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part due to consumption of foods contaminated with aflatoxins, which require metabolic activation to become carcinogenic. In a randomized, placebo-controlled, double-blind phase IIa chemoprevention trial, we tested oltipraz, an antischistosomal drug that has been shown to be a potent and effective inhibitor of aflatoxin-induced hepatocarcinogenesis in animal models. METHODS: In 1995, 234 adults from Qidong were enrolled. Healthy eligible individuals were randomly assigned to receive by mouth 125 mg oltipraz daily, 500 mg oltipraz weekly, or a placebo. Sequential immunoaffinity chromatography and liquid chromatography coupled to mass spectrometry or to fluorescence detection were used to identify and quantify phase 1 and phase 2 metabolites of aflatoxin B1 in the urine of study participants. Reported P values are two-sided. RESULTS: One month of weekly administration of 500 mg oltipraz led to a 51% decrease in median levels of the phase 1 metabolite aflatoxin M1 excreted in urine compared with administration of a placebo (P = .030), but it had no effect on levels of a phase 2 metabolite, aflatoxin-mercapturic acid (P = .871). By contrast, daily intervention with 125 mg oltipraz led to a 2.6-fold increase in median aflatoxin-mercapturic acid excretion (P = .017) but had no effect on excreted aflatoxin M1 levels (P = .682). CONCLUSIONS: Intermittent, high-dose oltipraz inhibited phase 1 activation of aflatoxins, and sustained low-dose oltipraz increased phase 2 conjugation of aflatoxin, yielding higher levels of aflatoxin-mercapturic acid. While both mechanisms can contribute to protection, this study highlights the feasibility of inducing phase 2 enzymes as a chemopreventive strategy in humans.

Acetylcysteine↗

PubMed1999

Dietary clay in the chemoprevention of aflatoxin-induced disease.

Aflatoxins are harmful by-products of mold growth and, though invisible to the naked eye, are potentially fatal. The aflatoxin problem is long-standing and inextricable. Concerns about the aflatoxins originate from the strong implications of their involvement in disease and death in humans and animals, yet scientists and clinicians are still seeking ways to effectively deal with these dangerous and elusive chemicals. Safe, practical, and effective strategies for the detoxification of aflatoxin-contaminated food and feed are highly desirable. A simple and effective approach to the chemoprevention of aflatoxicosis has been to diminish or block exposure to aflatoxins via the inclusion of HSCAS clay in the diet. HSCAS clay acts as an aflatoxin enterosorbent that tightly and selectively binds these poisons in the gastrointestinal tract of animals, decreasing their bioavailability and associated toxicities. Further studies to delineate the molecular mechanisms of action have shown that the dicarbonyl system of aflatoxin is essential for tight binding by HSCAS. In these studies, adsorption data was fitted to multiple isotherm equations including the Langmuir, multi-Langmuir, general Freundlich, Langmuir-Freundlich, Toth and various transforms. Information derived included: the Gibbs standard free energy change of adsorption, enthalpy of adsorption, capacity, affinity, and heterogeneity coefficient. Computer modeling was also utilized to provide additional structural information and insight into the mechanism. Evidence suggests that aflatoxins may react at multiple sites on HSCAS particles, especially the interlayer region, but also at edges and basal surfaces. Since clay and zeolitic minerals comprise a broad family of functionally diverse chemicals, there may be significant hidden risks associated with their indiscriminate inclusion in the diet. All aflatoxin binding agents should be rigorously tested, paying particular attention to their effectiveness and safety in aflatoxin-sensitive animals and their potential for interactions with critical nutrients.

Aflatoxins↗

PubMed1975

Translational step inhibited in vivo by aflatoxin B1 in rat-liver polysomes.

Aflatoxin B1 strongly inhibits protein synthesis in rat liver cells. We previously demonstrated that this inhibition could be divided into two steps: up to 5 h aflatoxin blocks protein synthesis directly and specifically at the polysome level; beyond 7 h protein synthesis inhibition appears chiefly as a consequence of transcription impairment due to drug action. This paper confirms the foregoing results and represents an attempt to localize the translational step inhibited in vivo by aflatoxin B1. We used the simulation study developed by Li, Kisilevsky, Wasan and Hammond, 1972 (Biochim. Biophys. Acta, 272, 451-462) to determine precisely the site inhibited in vivo after drug intoxication. This analysis is based on two parameters: the kinetics of polysome labeling to follow the nascent peptide synthesis, and the kinetics of supernatant labeling to follow the completed protein synthesis. Up to 5 h after dosing, aflatoxin specifically inhibits the elongation and/or termination steps during protein synthesis; after longer periods of time inhibition occurs essentially at the initiation step. When the intracellular concentration of aflatoxin is too high, particularly 2 h after dosing, each step of protein synthesis is blocked. Polypeptide synthesis by the postmitochondrial supernatants isolated from aflatoxin-treated animals is impaired in the same proportion as protein synthesis in vivo. The damage caused by aflatoxin is mostly observed on microsomes. However, purified polysomes isolated from aflatoxin-treated rats synthesize proteins in vitro to the same extent as those from controls. These results suggest that aflatoxin metabolite(s) are bound to polysomes with noncovalent bonds. These active metabolites are probably lost during polysome isolation procedures. Finally, relationships between protein metabolism and aflatoxin carcinogenesis are discussed.

Aflatoxins↗

PubMed1989

Foetal and neonatal exposure to aflatoxins.

Studies on 125 primigravidae in rural Kenya revealed aflatoxins in the blood of 54 prenatally. At delivery re-examination of 34 showed aflatoxins in 12 previously negative. The overall detection rate was 53%. Blood from additional 59 women collected at delivery showed aflatoxins in 53%. Aflatoxins were detected in 37% of 101 cord bloods. There was no relationship between aflatoxins in maternal and cord bloods. The frequency of detection was significantly higher in maternal and cord bloods during the 'wet' than 'dry' months. The mean birth weights of females born to aflatoxin positive mothers was significantly lower (255 g) than those born to aflatoxin free mothers. Two stillbirths were recorded, in both cases maternal and cord blood showed aflatoxins. These findings and the adverse effects of prenatal aflatoxin exposure recorded in animal experiments indicate the need for further study of the effects of aflatoxins on the human foetus and newborn.

Aflatoxins↗

PubMed1981

Production and characterization of aflatoxin B2a antiserum.

The specificity and sensitivity of antiserum elicited from rabbits against aflatoxin B2a-bovine serum albumin conjugates were characterized with a radioimmunoassay (RIA) and an enzyme-linked immunosorbent assay (ELISA). Aflatoxin B1 was first converted to aflatoxin B2a and then conjugated to bovine serum albumin and horseradish peroxidase by a reductive alkylation method. The antiserum was developed in New Zealand white rabbits by multiple-site injection with the aflatoxin B2a-bovine serum albumin conjugate. Antibody titers were determined by both RIA and ELISA. Competitive RIAs with various aflatoxin analogs indicated that the antiserum was most reactive with aflatoxin B1 and slightly cross-reactive with aflatoxins B2a, B2, and M1. Competitive ELISAs showed the antiserum to be equally specific for aflatoxins B2a and B12 and less reactive with aflatoxins B2 and M1. The relative sensitivities of RIA and ELISA for aflatoxin B1 quantitation were 100 and 10 pg per assay, respectively.

Aflatoxins↗

PubMed1995

A beta-glucuronidase reporter gene construct for monitoring aflatoxin biosynthesis in Aspergillus flavus.

Aflatoxins are toxic and carcinogenic secondary metabolites produced by the fungi Aspergillus flavus and A. parasiticus. Current research is directed at the elimination of these compounds in important food sources. The objective of this research was to develop a method to study the induction and regulation of aflatoxin biosynthesis by examining the expression of one aflatoxin pathway gene, ver1. The promoter region of ver1 was fused to the beta-glucuronidase (GUS) gene (uidA) from Escherichia coli to form the reporter construct, GAP13. A. flavus 656-2 was transformed with this construct. Aflatoxin production, GUS activity, and transcript accumulation were determined in transformants after shifting the cultures from a nonconducive medium to a medium conducive to aflatoxin biosynthesis. Transformants harboring GAP13 displayed GUS expression only when aflatoxin was detected in culture. Further, the transcription of the uidA gene driven by the ver1 promoter followed the same profile as for the ver1 genes. The results show that the GAP13 construct may be useful as a genetic tool to study the induction of aflatoxin in situ and to identify substances that affect the expression of genes involved in aflatoxin biosynthesis. The utility of this construct to detect inducers of aflatoxin biosynthesis in maize kernels was tested in a bioassay. A heat-stable inducer of aflatoxin with a molecular size of less than 10 kDa was detected in extracts from maize kernels colonized by A. flavus.

Aflatoxins↗

PubMed1980

Variation with age in response of broilers to aflatoxin.

This study investigated the effects on growth and composition of the blood of dietary aflatoxin fed at levels of 0, 2.5, or 5.0 microgram/g of diet for a three week period beginning at 1, 7, 14, and 21 days of age in commercial broilers. Packed cell volume (PCV), erythrocyte counts, mean corpuscular volume, hemoglobin content and mean corpuscular hemoglobin concentration, body weight, and mortality were measured weekly. Plasma cholesterol and total plasma protein levels were determined weekly. Dietary aflatoxin at levels of 2.5 and 5.0 microgram of aflatoxin per gram of diet when fed to young chicks for three weeks, beginning at either one or seven days, depressed body weight and PCV in a dose related fashion. Body weight and PCV continued to be depressed by the 5.0 microgram/g diets in chicks treated from 2 to 5 weeks of age but not at the lower dosages. The feeding of aflatoxin at levels of up to 5.0 microgram aflatoxin per gram of diet from 3 to 6 weeks of age did not significantly depress body weight or PCV from control levels. Plasma cholesterol and total protein were found to be more sensitive to aflatoxin treatment at the later ages than body weight and other blood values. Plasma cholesterol was significantly depressed by the 5.0 microgram/g level of aflatoxin in all treatment periods, but the 2.5 mirogram/g level of aflatoxin did not significantly reduce cholesterol during the 3 to 6 week treatment period. Plasma proteins were found to be the most sensitive criteria for detecting broiler susceptibility to aflatoxin, being depressed by all levels of aflatoxin for all age groups.

Aflatoxins↗

PubMed2001

Survey of aflatoxin concentrations in wild bird seed purchased in Texas.

The use of backyard feeders to attract avian wildlife is a common practice throughout the United States. However, feeding wildlife may create a problem due to aflatoxin, a harmful fungal metabolite, which can affect wildlife that are fed contaminated grain. Our study was initiated to determine if songbirds were being exposed to aflatoxin-contaminated feed throughout Texas. Bags of wild bird seed (n = 142) were purchased from grain cooperatives, grocery stores, and pet shops located in the panhandle, central, south, east, and west regions of Texas during spring and summer 1999. Aflatoxin concentrations in bird seed ranged from non-detectable to 2,780 micrograms/kg. Overall, 17% of samples had aflatoxin concentrations greater than 100 micrograms/kg, of which 83% contained corn as an ingredient. Retail establishment effects were noted in the southern and western regions of Texas, with average concentrations of aflatoxin greater from bags of bird seed purchased from grain cooperatives, followed by pet shops, then grocery stores. Regional differences in aflatoxin levels were not apparent from bags of seed purchased at pet shops: however, regional differences were noted in aflatoxin levels from seeds obtained at grocery stores and grain cooperatives. Average aflatoxin concentration from seed purchased at grocery stores was greatest in the panhandle region, followed by the remaining regions. Within grain cooperatives, the panhandle, south, and west regions of Texas exhibited higher levels of aflatoxin-contaminated bird seed than cooperatives within the east and central regions of Texas. Granivorous songbirds in Texas are exposed to aflatoxins at backyard feeders, which may be a significant morbidity and mortality factor.

Aflatoxins↗

PubMed1975

Reduction of aflatoxins B1 and B2 with sodium borohydride.

Reduction of aflatoxin B1 and aflatoxin B2 with sodium borohydride quantitatively yielded new fluorescent derivatives, designated as aflatoxin RB1 and aflatoxin RB2. Mass spectrometric data showed that RB1 and RB2 were trihydroxy derivatives of B1 and B2, respectively. Nuclear magnetic resonance analysis revealed that new chemical shifts were present in aflatoxins RB1 and RB2 in addition to those of the parent aflatoxins. The new compounds had lower melting points and different ultraviolet and infrared spectra compared to aflatoxins B1 and B2 and the monohydroxy derivative aflatoxicol. They were lses toxic to chick embryos than the parent toxins. Since the reduction yields were quantitative and since the reduction products could be detected at low levels comparable to those for B1 and B2, the reduction reaction could be used as a confirmatory test for both aflatoxins B1 and B2. Preliminary results obtained from gas-liquid chromatography (GLC) analysis of the trimethylsilyl derivatives of aflatoxins RB1 and RB2 indicated that these compounds could furnish the basis for developing an analytical GLC method for aflatoxins B1 and B2.

Aflatoxins↗

PubMed2005

Occurrence of aflatoxin in some of the food and feed in Nepal.

BACKGROUND: There are many contaminants like aflatoxin present in food products. Aflatoxin in comparison to many other contaminants is very toxic and also carcinogenic. There are reports of outbreak of aflatoxin toxicity in many parts of the world. AIM: To find out the level of aflatoxin in common food and feed. SETTING: The study was conducted in 16 districts of the Eastern region of Nepal. METHODS AND MATERIALS: Samples were collected from retailers and whole sellers from 1995 to 2003. Common food items that had high chances of infestation were collected. Food sample were taken to the laboratory to estimate the level of aflatoxin. The thin layer chromatography method was used to detect aflatoxin in the samples and comparison of fluorescence of sample spot with fluorescence of standard for estimation. RESULT: There were 832 samples for aflatoxin detection and estimation. One-third samples were found to be contaminated with aflatoxin. The highest percentage of contamination was found in peanut butter/vegetable oil (42.5%) and the lowest in areca nut (25%). Highest proportion of cornflakes samples were found to be contaminated with aflatoxin by more than the recommended value (30 ppb) and contamination in peanut was the lowest. CONCLUSION: People consume many common food items that contain aflatoxin. It is of high importance for the concerned department to give attention to this important public health issue. Even in small doses, continuous consumption can lead to many health problems. So it is of paramount importance to detect and control these contaminants in food items.

Aflatoxins↗

PubMed2006

[Surveillance on contamination of total aflatoxins in corn, peanut, rice, walnut and pine nut in several areas in China].

OBJECTIVE: To realize the contamination of total aflatoxins in corn, peanut, rice, walnut and pine nut in China, and provide the base data for establishing a China tolerance limit standard and an international control practice for total aflatoxins. METHODS: The samples of corn, peanut, rice, walnut and pine nut from Chongqing, Fujian, Guangdong, Guangxi, Hubei, Jiangsu, Shanghai and Zhejiang provinces and municipalities were collected randomly from markets, with the totally 284 samples. The samples were grounded and added to acetonitrile/water mixture. After filtering, the extract was transferred into a purifying column and pressed slowly. Then the purified liquid was derivatized with trifluoroacetic acid (TFA) and detected by using a high performance liquid chromatography (HPLC). RESULTS: There was 70.27% corn having been detected out an average level of aflatoxins of 36.51 microg/kg and the highest level was 1098.36 microg/kg. At the same time, there was 14.86% corn exceeding the China national tolerance limit. In peanut, the aflatoxins detected rate was 24.24%. The average level was 80.27 microg/kg and the highest level was 437.09 microg/kg. While there was 3.03% peanut exceeding the China national and Codex tolerance limits. All of the rice, walnut and pine nut samples met the China tolerance limit for aflatoxins. CONCLUSION: Corn and peanut might be the severely contaminated foods with aflatoxins in China. The aflatoxin B(1) in foods might be can not delegate the contamination of aflatoxins completely. Surveillance of total aflatoxins in foods suggested an actual need of establishing the China national and international standards for total aflatoxins.

Aflatoxins↗

PubMed1975

Influence of carbon tetrachloride or riboflavin on liver carcinogenesis with a single dose of aflatoxin b1.

Liver carcinogenesis with a single dose of aflatoxin B1 (7 mg/kg body weight) has been investigated in a group of female Wistar strain rats by repeated biopsies and necropsies. Another group received a subsequent intoxication with carbon tetrachloride by inhalation (approximately 200 doses) and another one was overloaded with riboflavin (25 parts/10(6) in drinking water). The frequency of hepatomata was almost equal in the aflatoxin and aflatoxin-carbon tetrachloride group. It was lowere in the riboflavin-aflatoxin group. In these 3 groups cirrhosis was never present in neoplastic livers. Megalocytosis was the first lesion observed. All tumoral livers had previous or concomitant megalocytosis. This modification was about as frequent, intense and widespread in aflatoxin-CCl4 and aflatoxin groups but appeared much earlier, as did the first hepatoma, in the aflatoxin-CCl4 group. It was less frequent, less intense and less widespread in the riboflavin-aflatoxin group than in the aflatoxin group. There was also a lower frequency of hepatomata in the riboflavin-aflatoxin group, but the difference was not significant due to the too small number of animals involved. The facts are not a proof of the existence of an obligatory link between megalocytosis and carcinogenesis since a slight megalocytosis was observed in the riboflavin group not affected by the neoplastic process. However, the simplest explanation of our results would be to consider that the potential tumour cells are located among the megalocytic cells, without admitting that every megalocyte is obligatorily a precancerous cell. CCl4 seems to act in shortening the time of appearance of megalocytosis. The protective effect of riboflavine should be regarded with more caution.

Aflatoxins↗

PubMed1982

[The effect of long term administration of aflatoxins on the health status of male rats and pigs with respect to morphological changes in the testes].

Long-continued administration of differentiated doses of aflatoxins was studied as to its effect on the over-all health conditions of male rats and pigs. Crude extract of the toxicogenic strain of Aspergillus flavus and was used for the experiments. The amount of aflatoxins is related to the actual content of aflatoxin B1, determined fluorometrically. Feed containing 1.0 mg aflatoxin per kg was administered in feeding trials with rats. Differentiated concentrations (20.0, 4.0, 2.0 and 0.2 mg aflatoxin B1 per day for 211 days) in feed were used in adult boars. After a longer time of administration, rats showed worse health condition and morphological changes corresponding to chronic aflatoxicosis. Serious changes were found during the histological examination of testes, including regressive changes of different intensity in the germinal epithelium of tubules, in some cases resulting in severe dystrophic alterations leading up to complete devastation of the spermiogenic epithelium. Interstitial tissue was considerably oedematous. Clinical manifestation of aflatoxicosis was observed in the boars given 20.0 mg aflatoxin B1 daily. When lower doses of aflatoxin were administered, no clinical manifestation of intoxication was recorded. In all cases, though no clinical disease occurred, feed conversion was impaired and weight gains decreased, depending directly on aflatoxin doses. The health condition was evaluated objectively by haematological examination and by the determination of clinico-biochemical values in blood plasma. The pathoanatomic changes indicated chronical aflatoxicosis. Histological changes in the testes of boars given 4.0 and 20.0 mg aflatoxin B1 daily in feed occurred within 63 to 190 days. The testes showed different degrees of dystrophy leading to the destruction and atrophy of spermiogenic epithelium and to oedema in the tissue. The extent of the histological changes testifies to a significant damage caused to the spermiogenic epithelium of seminiferous tubules after long-continued administration of high doses of aflatoxins.

Aflatoxins↗

PubMed1993

A comparison of the effects of aflatoxin B1 on the livers of rats and duck hepatitis B virus-infected and noninfected ducks.

A need exists for an appropriate animal model for the involvement of both hepatitis B virus infection and ingestion of aflatoxins in the etiology of liver cancer. Duck hepatitis B virus-infected ducks, on the basis of hepatoma development in the wild in China, appear to offer this possibility. The duck has been reexamined as a model system, and key metabolic processes have been assayed in comparison with the rat model for hepatocarcinogenesis. Aflatoxin B1 was found to be more actively metabolized by hepatic microsomes isolated from Pekin ducks in vitro to the aflatoxin B1-8,9-epoxide than corresponding fractions from the rat, and in vivo, higher levels of aflatoxin B1-guanine adduct were formed in hepatic DNA than in the livers of the aflatoxin B1-sensitive F344 rat. Repair of this DNA lesion in the duck and the subsequent formation of the ring-opened aflatoxin B1-FAPy adduct paralleled that in the rat. No effect of duck hepatitis B virus infection was found on any of these biochemical processes. The formation of hepatic lesions was also studied, and lesions were compared with those seen in the aflatoxin B1-treated rat. Histological analysis of necropsy specimens from ducks, 20 mo after the ducks received doses of aflatoxin B1 (25 and 50 micrograms/kg body wt), showed almost complete regression of the early acute lesions, with no evidence of neoplasia. Male F344 rats treated with aflatoxin B1 150 micrograms/kg 5 days/wk for 4 wk had extensive bile duct hyperplasia at the end of the treatment period and 100% incidence of hepatocellular carcinoma after 52 wk. The possible basis for the relative sensitivity of ducks and rats to the carcinogenic action of aflatoxin B1 is discussed.

Aflatoxin B1↗

PubMed1984

Effect of aflatoxin B1 and major metabolites on phytohemeagglutinin-stimulated lymphoblastogenesis of bovine lymphocytes.

Effects of aflatoxin B1 and three of its metabolites on cellular immune response were assessed with an assay based on inhibition of tritiated thymidine uptake by phytohemeagglutinin stimulated lymphocytes. In this in vitro system aflatoxin B1 and aflatoxin Q1 were strongly inhibitory (more than 50% inhibition) at concentrations of 10 mu/ml, whereas aflatoxicol and aflatoxin B2 alpha exhibited little inhibition at 10 micrograms/ml and only 45 to 50% inhibition at 25 micrograms/ml. Contrasts with single degrees of freedom and orthogonal polynomial analysis revealed that the pair of aflatoxin B1 and aflatoxin Q1 differed linearly and quadratically from the pair of aflatoxin B2 alpha and aflatoxicol, but within each pair there were no differences. Limited data with aflatoxin M1 revealed that it was slightly more active than aflatoxicol in the assay, but minimal replication prevented rigorous statistical testing. It may be theorized that the moderate to strong inhibition of blastogenesis by aflatoxin B1 and its metabolites could inhibit T lymphocyte functions, such as killer, helper, effector, or other immune processes, and thus compromise the immunological surveillance mechanism.

Aflatoxin B1↗

PubMed1986

Clinical and pathologic changes in acute bovine aflatoxicosis: rumen motility and tissue and fluid concentrations of aflatoxins B1 and M1.

Effects of aflatoxin on bovine rumen motility were determined by radiotelemetric techniques. Aflatoxin altered amplitude and/or frequency of rumen contractions in steers given dosages of 0.2, 0.4, 0.6, or 0.8 mg of aflatoxin/kg of body weight. Effects of aflatoxin on rumen motility were dose dependent. An increase in elimination time of aflatoxin from rumen contents was observed in steers given the aflatoxin dosages of 0.4 to 0.8 mg/kg. The increase in elimination time of this toxin facilitates diagnostic capabilities for detecting bovine aflatoxicosis by obtaining rumen contents for analysis for aflatoxin. Aflatoxin M1 was detected in rumen contents from steers at 2 hours after aflatoxin was administered. Thus, intraruminal metabolism of aflatoxin B1 to M1 may occur.

Acute Disease↗

PubMed1990

Neonatal diethylstilbestrol treatment alters aflatoxin B1-DNA adduct concentrations in adult rats.

Aflatoxin B1-DNA adduct concentrations were measured in the livers of adult Sprague-Dawley CD rats treated on days 2, 4, and 6 postnatally with 1.45 mumols of diethylstilbestrol and in adulthood with phenobarbital, 3-methylcholanthrene, or vehicle prior to treatment with aflatoxin B1. Aflatoxin B1 (1 mg/kg) was injected 5 hr prior to killing the rats. Female rats exposed neonatally to diethylstilbestrol had significantly higher aflatoxin B1-DNA adduct concentrations (three- to sixfold) than adult female rats treated neonatally with propylene glycol. Liver aflatoxin B1-DNA adduct concentrations were slightly higher in control males as compared to adduct concentrations in neonatally diethylstilbestrol-treated males, as compared to adduct concentrations in control females (not significant [NS]). Phenobarbital and 3-methylcholanthrene treatment followed by aflatoxin B1 injection resulted in decreased aflatoxin B1-DNA adduct concentrations in all rats. Our results demonstrate that neonatal exposure to diethylstilbestrol alters the capacity of adult female rats to form and/or dispose of carcinogen-DNA adducts following a single dose of aflatoxin B1 (increased adduct concentration). This alteration may be a consequence of altered imprinting mechanisms with diethylstilbestrol causing developmental modifications early in life. The animals were, however, able to respond to cytochrome P-450 and P-448 inducers as evidenced by decreased aflatoxin B1-DNA adduct concentrations.

Aflatoxin B1↗

PubMed1990

Aflatoxin B1 metabolism by 3-methylcholanthrene-induced hamster hepatic cytochrome P-450s.

We have studied the activation of aflatoxin B1 by hamster liver microsomes and purified hamster cytochrome P-450 isozymes using a umu mutagen test. The hamster liver microsomes or S-9 fractions were much more active than rat liver microsomes or S-9 fractions in the activation of umu gene expression by aflatoxin B1 metabolites. 3-Methyl-cholanthrene treatment increased aflatoxin B1 activation by hamster liver microsomes. Two major 3-methylcholanthrene-inducible cytochrome P-450 isozymes, P-450 MC1 (IIA) and P-450 MC4 (IA2), were purified from 3-methylcholanthrene-treated hamster liver microsomes, and the metabolism of aflatoxin B1 by these two cytochromes was studied. In the reconstituted enzyme system, both P-450 MC1 and P-450 MC4 were highly active in the activation of aflatoxin B1, and antibodies against these P-450s specifically inhibited these activities. Antibody against P-450 MC1 inhibited the activation of aflatoxin B1 by 20% in the presence of 3-methyl-cholanthrene-treated hamster liver microsomes. In contrast, antibody against P-450 MC4 stimulated the activity by 175%. These results indicated that hamster P-450 MC1 might convert aflatoxin B1 to more toxic metabolite(s), whereas P-450 MC4 might convert aflatoxin B1 to less toxic metabolite(s), than aflatoxin B1 in liver microsomes. The metabolite(s) produced by both hamster cytochrome P-450 MC1 and MC4 were genotoxic in the umu mutagen test.

Aflatoxin B1↗