Zearalenone (ZEA), a mycoestrogen produced by Fusarium fungal species, is mainly found in contaminated corns and maize. Despite ZEA has been reported in air and waters, little is known about the toxic effects induced by ZEA in vitro or in vivo. As ZEA has a similar structure to estrogen, its potential risk as an endocrine disrupting chemical (EDC) has thus aroused both environmental and public health concerns. The purpose of the first part of the study is to identify the responses and underlying molecular changes that occur when human bronchial epithelial BEAS-2B cells are exposed to ZEA. Differential gene expression profiles were identified in cells that were treated with 40μM ZEA for 6h and 24h by high-throughput microarray analysis using Affymetrix Human Gene 2.0 GeneChip. The array results showed 262 genes at 6h and 1073 genes at 24h were differentially expressed (fold change ≥1.5, p<0.05). Pathway analysis of the differentially expressed genes revealed that diverse cellular processes, which include the induction of oxidative stress, impaired response to DNA damage, cell cycle arrest, suppression of inflammatory responses, altered responses of nuclear hormone receptors and epigenetic changes, were affected. esults of further experiments indicated that 40μM ZEA decreased cell viability, induced apoptosis and promoted reactive oxygen species (ROS) generation in a time-dependent manner. Immunomodulatory effects of ZEA were revealed through the suppression of lipopolysaccharide (LPS)-induced expression of pro-inflammatory cytokines (IL-6, IL-8 and IL-1β). Interestingly, the level of global DNA methylation was markedly decreased after 24h exposure to ZEA. In vitro study using BEAS-2B cell line over-expressing a free radical scavenger, cytoglobin, showed significant attenuation of ZEA-induced ROS and cell death confirming that ZEA is a potent free radical producer. Taken together, these observations suggested that a broad range of toxic effects are elicited by ZEA. Particularly, ROS may play a pivotal role in ZEA-induced cell death. These adverse consequences observed in lung cells suggest that exposure to ZEA may lead to the pathogenesis in lung tissues. Previous studies have shown that growth and reproduction of early life stages of fish are susceptible to a variety of EDCs. However, the ecotoxicological risk of ZEA to aquatic wildlife is still poorly understood. Using marine medaka (Oryzias melastigma) as a model, the disrupting effects of ZEA on the physio-biochemical and endocrine function in vivo were studied. No effects were observed on hatching success, time to hatching and mortality after incubation of medaka embryos with ZEA at sublethal concentration of 50μg/L. No changes were observed in the Bax/Bcl2 mRNA ratio or apoptotic patterns. These results suggest that ZEA do not affect the development of the medaka embryos. However, the expression of key steroidogenic enzymes (CYP19A, CYP19B) as well as known estrogenic biomarkers (ERβ and VTG) were up-regulated at mRNA levels in newly hatched fry, indicating ZEA can potentially cause endocrine disruption in fish and posed a risk on aquatic life. / published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

Thesis (M.S.)--University of Wisconsin--Madison, 1982. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 98-103).

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Alternaria tagetica is capable of producing phytotoxins in vitro. One toxin was identified as zinniol with: bioassays; thin-layer and gas chromatography; staining properties; ultraviolet and mass spectrometry, and nuclear magnetic resonance spectroscopy. The identity of the other toxin(s) has not been established. Symptoms similar to those caused by infection developed on detached marigold leaves treated with either of the toxins or synthetic zinniol. The toxins are not host selective. The distribution of zinniol among Alternaria species was studied. Thirty-one isolates of 10 pathogenic Alternaria spp. were tested for their ability to produce zinniol. Analyses were performed by gas-liquid and thin-layer chromatography. Of the seven pathogenic large-spored, long-beaked species tested A. carthami, A. macrospora, A. porri, A. solani, A. tagetica, and an unnamed isolate from Phaseolus vulgaris pods produced zinniol. A. brassicae, a non-pathogenic isolate of A. zinniae, and three pathogenic species lacking large-spores and long-beaks (A. alternata, A. citri, and A. raphani) did not produce zinniol. The quantity of zinniol produced varied greatly among species, among isolates of a single species, and between trials of the same isolate. All hosts of the Alternaria spp. tested were sensitive to zinniol at 50 to 200 micrograms/ml. Conservation of zinniol in pathogenic large-spored Alternaria spp. may be indicative of its importance in pathogenesis. Light affects the behavior of Alternaria tagetica in vitro and in vivo. In vitro zinniol production occurred only during active fungus growth in the light; in the dark zinniol production occurred primarily after growth stopped. In all filtrates, the quantity of zinniol rapidly declined once zinniol production ceased. Fungus growth was inhibited by both continuous and alternating light and sporulation occurred on one of three test media and only under alternating light. More lesions were produced on inoculated plants kept in dark humidity chambers than in illuminated humidity chambers. Low illuminance was more conducive to lesion development than high illuminance and more lesions developed on plants exposed to low illuminance for 48 hr prior to inoculation than on those exposed to high illuminance. The limitations of studies in which the effect of light has been overlooked are discussed.

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Thesis (Ph. D.)(Microbiology)--University of Pretoria, 2003. / Includes bibliographical references.

The inoculation of Aspergillus flavus spores into a culture of Streptococcus lactis in LTB medium resulted in none or little aflatoxin production even though growth of the fungus was not hindered. The drop in pH and reduced nutrients in the medium as the result of S. lactis growth were not the cause of the observed inhibition. The inhibition was not eliminated by the addition of carbohydrate equal to the amount utilized by the bacterium prior to the inoculation with the fungus. Aflatoxin production was also inhibited when S. lactis was inoculated after A. flavus had grown. In addition to inhibiting the synthesis of aflatoxin, S. lactis also degraded pre-formed toxin. Aflatoxin, on the other hand, not only reduced the growth of S. lactis but also affected the morphology of the bacterial cell--the cells became elongated and formed long chains. / S. lactis produced and excreted the inhibitor into the medium during the early stage of growth (4 h). The inhibitor was a heat stable low molecular weight compound (MW (LESSTHEQ) 500). Neither volatile (acetic) nor non-volatile (succinic and lactic) acids which were detected in extracts containing the inhibitor were responsible for this inhibition. Lactic acid was found in larger quantities in mixed cultures and its addition to mono fungus culture was found to stimulate aflatoxin production. Chloroform: methanol extraction of the S. lactis culture filtrate removed all the activity to the organic phase. Further, the active compound was insoluble in hexane, not extracted by sodium bicarbonate and was soluble in acetone, indicating a polar lipid. Autoradiographic studies showed that the inhibitor was a product of glucose metabolism. Further characterization indicated that the inhibitor was a phosphoglycolipid containing an aromatic ring structure. / Filtrate extracts of A. flavus grown in presence of S. lactis were toxic to Bacillus megaterium but did not exhibit mutagenic or carcinogenic activity in the Salmonella/Mammalian microsome mutagenicity test.