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PubMed1983

Restricted repair of aflatoxin B1 induced damage in alpha DNA of monkey cells.

We have investigated the processing of adducts formed by covalent binding of aflatoxin B1 (AFB1) to DNA in confluent cultures of African green monkey cells. Repair synthesis elicited by AFB1 adducts was deficient in alpha DNA sequences compared to that in bulk DNA, although the initial levels of modification were the same for these DNAs. The removal of the primary initial adduct, AFB1-N7-Guanine, was deficient in alpha DNA and the kinetics of its loss resembled those previously reported for removal from total DNA in xeroderma pigmentosum cells of complementation group A. Spontaneous loss of the AFB1 moiety or the concomitant loss of the guanine to yield an apurinic site account for these results. The formation of the more chemically stable secondary product, AFB1-triamino-Pyrimidine, occurred more rapidly and to a greater extent in alpha DNA than in bulk DNA, probably because of slower removal of the primary product. The excision repair patch size for AFB1 adducts in alpha DNA was only 10 nucleotides compared to 20 nucleotides for repair of AFB1 adducts in bulk DNA. Irradiation of cells with low doses of UV prior to or immediately after treatment with AFB1 increased the rate and extent of removal of AFB1 adducts from alpha DNA to the levels found in the bulk DNA, indicating that the formation of pyrimidine dimers or their repair may alter the chromatin structure of alpha DNA sufficiently to facilitate its repair.

Aflatoxin B1↗
PubMed1990

Disposition of 3H-aflatoxin B1 in mice: formation and retention of tissue bound metabolites in nasal glands.

Whole-body autoradiography with 3H-labelled aflatoxin B1 (3H-AFB1) in C57B1-mice showed a pronounced accumulation and retention of radioactivity in some nasal glands. At long survival intervals the labelling of the nasal glands was much higher than that of the liver. Experiments in vitro showed a capacity of the nasal glands to form tissue-bound 3H-AFB1-metabolites. Incubations in the presence of glutathione decreased the levels of tissue-bound 3H-AFB1-metabolites both in the liver and in the nasal glands, but the decrease was more pronounced in the former than in the latter tissue. The 3H-AFB1-metabolite-binding to the nasal glands in vitro was inhibited by the cytochrome P-450-inhibitor metyrapone and by CO- and N2-atmospheres indicating a cytochrome P-450-dependent bioactivation of the AFB1 in these glands. Cytochrome P-450 was shown to be present in the glands although at a much lower level than in the liver. The glands in the nose, which were shown to have this AFB1-metabolizing capacity, were the lateral nasal gland (Steno's gland) situated ventrally and laterally to the maxillary sinus and the large group of glands in the lateral nasal wall ventrally to the ostium of the maxillary sinus. Our results also indicated an AFB1-metabolizing capacity of the serous glands which are present in the anterior part of the nasal septum.

Aflatoxin B1↗
PubMed1986

Comparative ultrastructural effects of aflatoxin B1 on mouse, rat, and human hepatocytes in primary culture.

Human, rat, and mouse hepatocytes in primary culture were treated with aflatoxin B1 (AFB1) and examined for ultrastructural alterations. As early as 1 h following in vitro exposure to AFB1, there were ultrastructural changes in the nuclei of rat and human hepatocytes. The most prominent change in the nuclei was a segregation of nucleolar components that resembled the segregation in liver cells of rats exposed to AFB1 in vivo. The nucleolar segregations were developed by incubating rat hepatocytes for 24 h in a medium containing as little as 0.01 micrograms of AFB1 per ml. The minimum concentration to induce the same change in human hepatocytes was 0.1 micrograms/ml. No distinct nucleolar alteration was observed in mouse hepatocytes incubated in a medium containing 10 micrograms of AFB1 per ml. Irregular nuclear chromatin condensation also developed in the cells exposed to a higher concentration of AFB1, whereas little damage was observed in mitochondria and lysosomes. The similarity in morphological changes between our in vitro model and in vivo models previously investigated indicates that the hepatocytes in primary culture maintain the biological properties necessary for carcinogen responses similar to liver cells in vivo. In addition, the morphological changes in cultured rat and mouse hepatocytes induced by AFB1 correlate with in vivo experiments insofar as mice are relatively resistant, whereas rats are sensitive to AFB1 carcinogenesis. Thus, cultured hepatocyte systems may be a valuable tool to study genetic damage which may lead to hepatocellular carcinomas in human and animal livers.

Aflatoxin B1↗
PubMed1987

Comparative effects of butylated hydroxyanisole on hepatic in vivo DNA binding and in vitro biotransformation of aflatoxin B1 in the rat and mouse.

To determine the mechanisms which mediate species- and treatment-related differences in susceptibility to aflatoxin B1 (AFB), we conducted a comparative study of the effects of dietary butylated hydroxyanisole (BHA) on the hepatic in vivo DNA binding and in vitro biotransformation of AFB in the rat and mouse. Mice are resistant to the hepatocarcinogenic effects of AFB, and BHA pretreatment has been shown to inhibit the carcinogenic effects of AFB in the highly susceptible rat. Rats and mice were fed a control diet or an identical diet containing 0.75% BHA for 10 days. On the 11th day, one-half of the control and BHA animals were administered [3H]AFB (0.25 mg/kg in dimethyl sulfoxide) via intraperitoneal injection. Animals were killed 2 hr later and covalent binding of AFB to hepatic DNA was determined. The remaining animals were killed for preparation of hepatic subcellular fractions used in in vitro assays. BHA treatment resulted in a decrease in in vivo hepatic AFB-DNA adduct formation in mice to 68% of control, but, in rats, treatment decreased AFB-DNA binding to 18% of control. Furthermore, hepatic AFB-DNA binding in control mice was only 1.2% of that measured in control rats. The rate of in vitro activation of AFB to the epoxide was 3.4-fold greater in control mice relative to control rats. BHA pretreatment increased the activation of AFB in mice 3.3-fold, but had no effect on oxidative metabolism in rats. Control mice had 52 times greater glutathione S-transferase (GST) activity toward the AFB-epoxide, but only 2.6 times greater GST activity toward 1-chloro-2,4-dinitrobenzene (CDNB), compared to that of control rats. In mice, BHA did not significantly increase GST activity toward the AFB-epoxide, but increased GST activity toward CDNB 3.1-fold. In rats, BHA increased GST activity toward the AFB-epoxide and CDNB by 3.2- and 2.1-fold, respectively. Epoxide hydrolase activity toward p-nitrostyrene oxide in mice was only 52% of the activity in rats. BHA increased epoxide hydrolase activity 3.8- and 2.5-fold in mice and rats, respectively. These data indicate that mice have high levels of an AFB-epoxide-specific GST activity relative to that of the rat. The rate of formation of the AFB-epoxide and the activity of epoxide hydrolase appear to be relatively unimportant under conditions of high GST activity, whereas elevated GST activity, and thus inactivation of the AFB-epoxide, appears to be the critical component in species- and BHA-induced differences in AFB-DNA adduct formation and, presumably, AFB hepatocarcinogenicity.

Aflatoxin B1↗
PubMed1980

Effect of partial hepatectomy on the response of rat liver to aflatoxin B1.

The effect of partial hepatectomy (PH) on aflatoxin B1 (AFB1) action in rat liver has been examined using adult male Fischer 344 rats. The elevated levels of hepatic DNA synthesis, present 26 hr after PH (> 15 times the control level) and 33 hr after PH, are rapidly inhibited by i.p. administration of AFB1. The percentage inhibitions are greater than those observed using intact or sham-operated animals. However, it was possible to demonstrate elevation of DNA synthesis in PH rats treated with AFB1. Rats 2 hr after being treated with AFB1 (0.075 mg/kg) at 24 and 31 hr after PH exhibited levels of DNA synthesis 380 to 400% of those present in sham-operated uninjected controls. After 62 weeks, the livers of the PH rats treated with AFB1 displayed no hepatocellular carcinoma. There was present, however, an increased incidence of lesions believed to be preneoplastic. The differences between the long-term effects of AFB1 and other hepatocarcinogens on the livers of PH rats are discussed in terms of their relative capacities and modes of action in inhibiting DNA synthesis.

Aflatoxins↗
PubMed1988

The in vitro porcine brain tubulin assembly assay: effects of a genotoxic carcinogen (aflatoxin B1), eight tumor promoters and nine miscellaneous substances.

Aflatoxin B1 (AFB1) had a reversible inhibitory effect on the assembly of porcine brain tubulin in vitro. The 30%-inhibition concentration was 0.3 mM AFB1. The 8 tumor promoters showed different effects. Five of them, anthralin, cholic acid, gamma-hexachlorocyclohexane (lindane, gamma-HCH), lithocholic acid and phenobarbital (PB), enhanced the in vitro assembly. The effect was reversible in the case of PB and anthralin, only partially reversible in the case of cholic acid and gamma-HCH, whereas the stimulating effects of lithocholic acid led to an irreversible modification of the tubulin structure, as shown by the insolubility of the microtubules at 0 degrees C. This could be confirmed by an electron microscopic study. The doses necessary for a 30% enhancement of the steady-state level were 3 mM (PB), 0.2 mM (anthralin), 6 mM (cholic acid), 0.7 mM (gamma-HCH) and less than 0.2 mM (lithocholic acid). The other 3 tumor promoters tested - diethylstilbestrol (DES), 4,4'-dichloro-diphenyl-trichloro-ethane (DDT) and saccharin - inhibited the assembly. The concentrations necessary for a 30% inhibition varied within a wide range: 0.025 mM, 0.4 mM and 7.5 mM for DES, DDT and saccharin, respectively. Five of the 9 miscellaneous compounds, namely asbestos (crocidolite), bavistan, colchicine, chloropropham and ethylacetate, showed inhibitory effects, whereas Fe2+ (a constituent of asbestos) and 5-azacytidine did not influence the assembly process. The 30%-inhibition concentrations for colchicine, ethylacetate and asbestos were 10 microM, 0.153 M and 0.19 mM, respectively. For bavistan and chloropropham the 30%-inhibition values were 0.7 mM and 2.0 mM, respectively. The inhibitory effects of chloropropham and asbestos were reversible. For colchicine and bavistan the reversibility of the effects was not assayed. In agreement with published data, dimethylsulfoxide (DMSO) and acetone enhanced the in vitro assembly of porcine brain tubulin. The doses needed for a 30% enhancement by DMSO and acetone were 0.4 mM and 0.136 M, respectively. The effect of DMSO was irreversible whereas acetone led to a reversible stimulation. Some compounds were tested for their influence on preformed microtubules (interaction with the equilibrium between assembly and disassembly). Anthralin, cholic acid, PB and DMSO showed no effect on the steady-state plateau. A slight reduction was induced by DDT and bavistan, whereas DES, colchicine and chloropropham led to a pronounced reduction.

Aflatoxins↗
PubMed2003

Identification of aflatoxin M1-N7-guanine in liver and urine of tree shrews and rats following administration of aflatoxin B1.

Epidemiological studies have shown that exposure to aflatoxin B(1) (AFB(1)) and concurrent infection with hepatitis B lead to a multiplicative risk of developing liver cancer. This chemical-viral interaction can be recapitulated in the tree shrew (Tupia belangeri chinensis). As an initial characterization of this model, the metabolism of AFB(1) in tree shrews has been examined and compared to a sensitive bioassay species, the rat. Utilizing LC/MS/MS, an unreported product, aflatoxin M(1)-N(7)-guanine (AFM(1)-N(7)-guanine), was detected in urine and hepatic DNA samples 24 h after administration of 400 microg/kg AFB(1). In hepatic DNA isolated from tree shrews, AFM(1)-N(7)-guanine was the predominant adduct, 0.74 +/- 0.14 pmol/mg DNA, as compared to 0.37 +/- 0.07 pmol/mg DNA of AFB(1)-N(7)-guanine. Conversely, in rat liver, 6.56 +/- 2.41 pmol/mg DNA of AFB(1)-N(7)-guanine and 0.42 +/- 0.13 pmol/mg DNA of AFM(1)-N(7)-guanine were detected. Rats excreted 1.00 +/- 0.21 pmol AFB(1)-N(7)-guanine/mg creatinine and 0.29 +/- 0.10 pmol AFM(1)-N(7)-guanine/mg creatinine as compared to 0.60 +/- 0.12 pmol AFB(1)-N(7)-guanine/mg creatinine and 0.69 +/- 0.16 pmol AFM(1)-N(7)-guanine/mg creatinine excreted by the tree shrew. Furthermore, tree shrew urine contained 40 times more of the hydroxylated metabolite, AFM(1), than was excreted by rats. In vitro experiments confirmed this difference in oxidative metabolism. Hepatic microsomes isolated from tree shrews failed to produce aflatoxin Q(1) or aflatoxin P(1) but formed a significantly greater amount of AFM(1) than rat microsomes. Bioassays indicated that the tree shrew was considerably more resistant than the rat to AFB(1) hepatocarcinogenesis, which may reflect the significant differences in metabolic profiles of the two species.

Administration, Oral↗
PubMed1986

Pulmonary interstitial fibrosis with evidence of aflatoxin B1 in lung tissue.

Three cases of pulmonary interstitial fibrosis, two in agricultural workers and one in a textile worker, are reported. In lung samples of all three patients the presence of aflatoxin B1 was demonstrated by radioimmunoassay (RIA). A possible occupational risk of aflatoxin exposure via the respiratory tract is suggested.

Aflatoxin B1↗
PubMed1983

Specificity of hepatic cytochrome P-450 isoenzymes from PCB-treated rats and participation of cytochrome b5 in the activation of aflatoxin B1.

Employing six forms of cytochrome P-450s fractionated from the hepatic microsomes of PCB-treated rats, the activation of aflatoxin B1 (AFB1) was examined in the reconstituted cytochrome P-450 system. AFB1 was specifically activated into DNA-binding form by cytochrome P-450 I-a, which is one of P-450 type cytochromes and possesses an absorption peak at 450.0 nm in its carbon monoxide difference spectrum. This activation was enhanced by cytochrome b5 and the maximal enhancement (1.6-fold of the control) was observed with the molar ratio of 0.25 cytochrome b5:1.0 cytochrome P-450.

Aflatoxin B1↗
PubMed1986

Endogenous promutagen activation in the yeast Saccharomyces cerevisiae: factors influencing aflatoxin B1 mutagenicity.

The formation of convertants, revertants and other types of mitotic segregants was induced in Saccharomyces cerevisiae D7 upon incubation with aflatoxin B1 (AFB1). The most distinct effects were observed for gene conversion to tryptophan prototrophy. The fact that different cytochrome P-450 inhibitors (ellipticine, penconazole and propiconazole as yeast-specific P-450 inhibitors) abolished the AFB1-induced mutagenicity indicates that activation of the promutagen AFB1 depends on the cytochrome P-450-catalyzed electron-transfer reactions. This hypothesis is further supported by the observation that the cytochrome P-450 content of yeast cells harvested at different phases during growth is directly correlated with their sensitivity for AFB1-induced tryptophan conversion.

Aflatoxin B1↗
PubMed1995

In vitro biotransformation of aflatoxin B1 (AFB1) in channel catfish liver.

The biotransformation of the dietary carcinogen aflatoxin B1 (AFB1) was examined in hepatic microsomal and cytosolic fractions from channel catfish, an aquatic species shown to be refractory to AFB1 toxicity and reported to be resistant to AFB1 hepatocarcinogenesis. Catfish liver microsomes catalyzed the in vitro oxidation of AFB1 to the reactive AFB1-8,9-epoxide (AFBO) at high substrate concentrations (128 microM AFB1) but not at low substrate concentrations (16 microM AFB1) which were more representative of environmental exposure. A similar trend was observed for the production of the hydroxylated metabolite aflatoxin M1 (AFM1). In contrast, hepatic microsomes prepared from rainbow trout, a species sensitive to AFB1 toxicity and hepatocarcinogenesis, activated AFB1 at 16 and 128 microM AFB1, with the rate of AFB1 epoxidation by trout microsomes exceeding that of catfish by more than sixfold. Treatment of channel catfish with 5,6-benzoflavone (beta NF, 20 mg/kg) resulted in a threefold increase in AFM1 formation but did not affect AFBO formation. AFB1 was rapidly reduced to aflatoxicol (AFL), a putative detoxification product of AFB1, at both low and high substrate concentrations. The rate of AFL production by channel catfish hepatic cytosol was 40- and 65-fold greater than observed for rainbow trout at 16 and 128 microM AFB1, respectively. Western blotting of catfish cytosols revealed the presence of a catfish cytosolic protein of approximately 25 kDa that displayed immunological cross-reactivity to rat GST Ya, but not to other rat or mouse alpha class GSTs with high AFBO-conjugating activity. Furthermore, catfish cytosolic GSTs did not catalyze the conjugation of AFBO with GSH. The results of these studies indicate that AFB1 is poorly oxidized by channel catfish microsomes, and suggest that the lack of microsomal AFB1 activation together with the rapid conversion of AFB1 to AFL contributes to the apparent resistance of channel catfish to AFB1 toxicity and hepatocarcinogenesis.

Aflatoxin B1↗
PubMed1984

The effect of phenobarbital pretreatment on the metabolism, covalent binding, and cytotoxicity of aflatoxin B1 in primary cultures of rat hepatocytes.

The effect of phenobarbital (PB) pretreatment on the metabolism, covalent binding, and cytotoxicity of [14C]aflatoxin B1 (AFB1) was studied in primary hepatocyte cultures. Hepatocytes from control and PB-pretreated rats were isolated from perfused liver biopsies and cultured in a chemically defined, hormone-supplemented medium. [14C]AFB1, dissolved in medium, was added to cultures at 20-22 h. The metabolism of AFB1 to water-soluble products and its binding to trichloroacetic acid-precipitable macromolecules were assessed 0.5 to 24 h later. At 6 h, PB pretreatment reduced total binding to macromolecules by 31% and reduced binding to RNA and DNA by 61% and 66%, respectively. In addition, PB protected cultures from the cytotoxic effects of AFB1, as evidenced by a significantly reduced (p less than 0.05) leakage of lactate dehydrogenase into the medium at 51 h. Elevated mixed-function oxidase and glutathione S-transferase activities, as well as higher levels of AFB1-glutathione conjugate were measured in cultures from rats pretreated with PB. The protective action of PB was concluded to be due to the induction of hepatic glutathione S-transferases responsible for the detoxification of AFB1.

Aflatoxin B1↗
PubMed1987

Modifying role of dietary factors on the mutagenicity of aflatoxin B1: in vitro effect of vitamins.

19 vitamins including some derivatives have been tested for their ability to suppress mutagenic activity of aflatoxin B1 (AFB1) towards Salmonella typhimurium strain TA100 activated with a rat-liver metabolic activation system. Several vitamins have shown an ability to inhibit the mutagenic potency of AFB1. The values of ID50, i.e. the dose required to inhibit mutagenic activity by 50% calculated from dose-response curves for each vitamin show retinoids, riboflavin, folic acid, menadione, cyanocobalamin, ascorbic acid and pyridoxine to be significantly antimutagenic. Although inhibition by vitamins is apparent over a range of AFB1 concentrations, their effect is more pronounced at lower concentrations of AFB1. When combined data are expressed in terms of specific mutagenicity, riboflavin, retinol and menadione have been found to possess exceptional inhibitory ability in as much as, on a molar basis, only 15-40-fold excess vitamins can inhibit the mutagenic potency of AFB1 by 50%. Their action is possibly mediated through interaction with microsomal activating enzymes. Previous evidence from this laboratory about their inhibitory action on DNA-adduct formation and metabolic activation together with the present results suggest that certain vitamins notably retinoids and riboflavin may have potential anticarcinogenic activity against AFB1.

Aflatoxin B1↗
PubMed1990

Cytotoxic effects of aflatoxin B1 and its association with cellular components in chicken embryo primary cultured cells.

We have examined the cytotoxicity and cellular incorporation of aflatoxin B1 (AFB1) in several types of established and primary cultured cells. The inhibition of DNA synthesis by AFB1 at 1 microgram/ml was about 0-30% in the established cell lines, including human hepatic cells. In chicken primary hepatocytes, however, DNA synthesis as well as RNA and protein syntheses were strongly inhibited by much lower concentrations of AFB1, e.g., 0.1 microgram/ml. In contrast, chicken primary fibroblasts showed almost no significant response to the toxin. Microsomal cytochrome P-450 activities in hepatic tissues were 10-20-fold higher than those in fibroblastic tissues. The amount of [3H]AFB1 incorporated into acid-insoluble materials in the primary hepatocytes was also 10-100-fold more than that in the primary fibroblasts. However, a significant amount of AFB1, which was enough to induce cytotoxic effects on the primary hepatocytes, could be incorporated into the primary fibroblasts when the concentrations of AFB1 were increased. Characterization of the AFB1-associated cellular components showed that most of them were DNA, RNA, and proteins in the primary hepatocytes, while in the primary fibroblasts a large portion of the incorporated AFB1 was recovered from lipid fractions. In addition, the selective binding of [3H]AFB1 to several proteins was observed only in the primary hepatocytes. The possible role of the AFB1-binding proteins are also discussed.

Aflatoxin B1↗
PubMed1987

Aflatoxin B1 and acetaminophen induce different cytoskeletal responses during prelethal hepatocyte injury.

Primary monolayer cultures of adult rat hepatocytes exposed to the hepatocarcinogen aflatoxin B1 (AFB1) undergo a characteristic prelethal cytomorphological change that is distinct from their response to the necrogenic noncarcinogenic hepatotoxin, acetaminophen (AAP). Since changes in cell shape are mediated, at least in part, by the F-actin cytoskeleton, we designed experiments to study early prelethal alterations in the distribution of actin microfilaments in monolayer rat hepatocytes exposed to AFB1 (100 microM) or AAP (16 mM). Using rhodamine-phalloidin fluorescence microscopy, we observed that normal hepatocytes showed a submembranous F-actin distribution with focal short microfilaments extending into filopodia along the periphery of the cell. Hepatocytes exposed to AFB1 for several hours exhibited retraction of their cytoplasm within a prominent circumferential peripheral band of F-actin microfilament bundles. Retraction of focal areas of peripheral cytoplasm was associated with an increased prominence of the radial F-actin-containing filopodia. Subsequently, there appeared peripheral blebs containing very little F-actin. Hepatocytes exposed to equivalently lethal concentrations of AAP initially remained structurally normal. After several hours, the cells exhibited a prominent polar aggregate of short microfilament bundles without the formation of blebs. Both the blebbing and the polar aggregation of F-actin bundles occurred prior to cell death as shown by lactate dehydrogenase release and trypan blue exclusion. These studies support the hypothesis that the lethal effects of these two agents may occur by different biological mechanisms that are associated with remarkably distinct prelethal cytoskeletal responses.

Acetaminophen↗
PubMed1987

Combined effects of the mycotoxins aflatoxin B1 and cyclopiazonic acid on Sprague-Dawley rats.

This study was conducted to determine whether exposure to cyclopiazonic acid (CPA) and aflatoxin B1 (AFB1) would alter the toxicity associated with exposure to either toxin individually. Groups of male rats were administered 0, 0.1 or 4.0 mg CPA/kg body weight/day intragastrically (three groups per dose level) for three consecutive days and 30 min after each of these CPA doses the rats were dosed by gavage with 0, 0.1 or 2.0 mg AFB1/kg body weight/day. Six of the 12 rats given each of these nine treatments were killed on day 4 after the initial dosing, and the rest were allowed a recovery period of 4 days prior to being killed. Weight loss in the three groups receiving 2.0 mg AFB1/kg/day occurred within 24 hr of the first doses. Feed consumption by these rats was about 60% of that in the other groups. By the end of the recovery period, rats in these three groups had lost an average of 31-38 g. Feed consumption throughout the recovery period by rats in the 2.0-mg AFB1 groups was about 50% of the control value, except in the group that also received the high dose of CPA, in which it was 75%. Gross pathological findings were primarily limited to rats in the high AFB1 group, and included icterus, shrunken liver and lesions in the kidney at the cortico-medullary junction. Microscopic changes were characteristic of aflatoxicosis in rats. Glycocholic acid assays indicated liver damage only in those groups that received the high AFB1 dose. We conclude that neither toxin potentiates the action of the other at the dose levels used in this study.

Aflatoxin B1↗
PubMed1998

Rearrangements in minisatellite sequences induced by aflatoxin B1 in a metabolically competent strain of Saccharomyces cerevisiae.

The role of aflatoxin B1 (AFB1) in the induction of rearrangements affecting minisatellite sequences was studied in an in vitro yeast model. The Saccharomyces cerevisiae strain used expresses human cytochrome P450 1A2 and NADPH-cytochrome P450 oxidoreductase and has previously been used to study genetic recombination events induced by AFB1. DNA multilocus fingerprinting was performed using probe M13 core hybridizing to a set of hypervariable minisatellite sequences in S. cerevisiae. Frequent spontaneous genomic alterations that affect the minisatellite fingerprint pattern were observed. Control cultures showed 15.8% rearrangements in minisatellites, and this frequency increased to 40.0% in cultures exposed to AFB1 (80 microg/ml). A total of approximately 29 minisatellite loci were visualized for each culture. Given the number of cultures examined (40 AFB1-treated and 38 controls) the rearrangement frequency per detectable minisatellite was 2.59% in the AFB1-treated group and 0.73% in the control group, which represents a statistically significant (P = 0.001) difference. Thus, our data strongly suggest that AFB1 can promote the genetic events responsible for minisatellite rearrangements in the yeast genome. Such genetic rearrangements may be important events during the etiology of liver carcinogenesis in people chronically exposed to dietary aflatoxins.

Aflatoxin B1↗
PubMed1976

Enzymatic conversion of sterigmatocystin into aflatoxin B1 by cell-free extracts of Aspergillus parasiticus.

A cell-free extract, prepared from Aspergillus parasiticus ATCC 15517 grown in synthetic medium, was active in converting [14C]sterigmatocystin into aflatoxin B1 in the presence of reduced nicotinamide adenine dinucleotide phosphate. The activity was demonstrated by the time course of conversion and the linear dependence of the yield of product on enzyme concentrations. Optimum activity was obtained at pH 7.5 to 7.8 at 27 C. The results confirm sterigmatocystin as a biogenetic precursor of aflatoxin B1. Techniques were developed for enzymatic studies on aflatoxin biosynthesis.

Aflatoxins↗