fusarin-c and Esophageal-Neoplasms

Topics: Animals; Carcinogens, Environmental; Edible Grain; Esophageal Neoplasms; Food Analysis; Food Contamination; Fumonisins; Humans; Mycotoxins; Polyenes

Fusarium moniliforme, a fungus of established carcinogenic potential, is one of the most common fungal contaminants of maize, millet and other grains in Linxian, China, a high-risk county for human esophageal cancer. Fusarin C, a major product of F. moniliforme grown on corn in the laboratory, is mutagenic in Salmonella tester strains and in V79 cells. Fusarin C treated rat esophageal epithelial cell line showed several characteristics of malignant transformations including the growth in nude mice. The present work demonstrated that Fusarin C can induce esophageal and forestomach carcinoma in DBA mice and Wistar rats thus further substantiating the carcinogenicity of this mycotoxin.

Topics: Animals; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Hyperplasia; Mice; Mice, Inbred DBA; Papilloma; Polyenes; Precancerous Conditions; Rats; Rats, Inbred Strains; Stomach Neoplasms

Fusarin C (FC) is a naturally occurring mutagen found on Fusarium moniliforme-contaminated corn. In Linxian, China, an area of exceptionally high incidence of esophageal cancer, the milled corn is made into small cakes called wotou, which are steamed. It has been suggested that FC may play a role in the etiology of esophageal cancer, but this has been questioned, in part, because of the thermal instability of FC. We therefore measured the effects of temperature on FC stability, mimicking the cooking process. FC was extracted from the wotou and quantitated by both reverse-phase high-performance liquid chromatography and the Ames assay. After wotou were steamed for 30 minutes, 11% and 3% of the initial FC remained, as detected by the two assays, respectively. The milled corn, when moistened with water, had a pH of 6.1, which was lowered to 5.3 when it was inoculated with F. moniliforme and cultured for three weeks. Pickled vegetables are sometimes added to the wotou, which further reduces the pH. To determine the effects of pH on FC, it was heated in solution, with the pH varied between 4 and 8. Its stability was very pH dependent, decomposing more rapidly as the pH increased. Because ingested FC would also be subjected to the low pH of the stomach, it was treated for 30 minutes at 37 degrees C and pH values ranging from 1.0 to 7.0. FC was stable (less than 15% decomposition) under these conditions. If FC is a significant health threat, it could most easily be destroyed by cooking at slightly basic pH values.

Topics: China; Chromatography, High Pressure Liquid; Cooking; Drug Stability; Esophageal Neoplasms; Humans; Hydrogen-Ion Concentration; Mutagens; Polyenes; Zea mays

Fusarin C (FC) is a mutagenic and carcinogenic mycotoxin which was isolated from Fusarium moniliforme culture extracts. The Fusarium moniliforme is one of most prevalent fungi found on corn in Linxian, a high risk area for esophageal cancer. This paper reports, for the first time, the malignant transformation of rat esophageal epithelial cells induced by FC. The transformed cells showed several characteristics of transformation. Colonies were formed after seeding these transformed cells either into selective medium free of epidermal growth factor (EGF) and serum, or on semi-solid agar; there was an increase in chromosome number; the expression of c-myc and v-erb-B oncogenes was enhanced in the cells; and squamous cell carcinomas arose after inoculating the cells into nude mice. The results demonstrated transforming effect of FC on rat esophageal epithelial cells, and indicate that the abnormal expression of some oncogenes could serve as a new property of transformed cells.

Topics: Animals; Cell Line; Cell Transformation, Neoplastic; Epithelial Cells; Esophageal Neoplasms; Esophagus; Gene Expression Regulation, Neoplastic; Genes, myc; Mice; Mice, Nude; Mutagens; Oncogene Proteins v-erbB; Oncogenes; Polyenes; Rats; Rats, Inbred Strains; Retroviridae Proteins, Oncogenic; Tetradecanoylphorbol Acetate

Fusarin C, a fungal metabolite, was recently isolated and identified from corn meal inoculated with Fusarium moniliforme which was one of the most common fungi associated with corn in Linxian county, a high-incidence area of esophageal cancer. In the presence of S-9 mix, fusarin C significantly increased the number of revertants in Salmonella typhimurium TA 100, and induced SCE, micronuclei, chromosome aberrations and 6-TG resistant mutants in V79 cells. The toxic action of fusarin C on V79 cells was much stronger in the absence of S-9 mix. However, fusarin C did not show, at the largest concentration used, any significant mutagenic or clastogenic effect on the cells without the addition of S-9 mix. The possible relationship between the consumption of corn contaminated with F. moniliforme and the cause of esophageal cancer was discussed.

Topics: Animals; China; Chromosome Aberrations; Cricetinae; Cricetulus; Esophageal Neoplasms; Fusarium; In Vitro Techniques; Mutagenicity Tests; Mutagens; Polyenes; Sister Chromatid Exchange; Zea mays