Studies On The Bioeffects And Carcinogenicity Of Sterigmatocystin In Vitro And In Vivo

ObjectivesSterigmatocystin (ST) is the toxic metabolite of Aspergillus versicolor and Aspergillus nidulans etc. It has been found that ST which has been proven mutagenic and carcinogenic to human and animal is one of the predominant contaminating mycotoxinsin in the foodstuffs of the residents in high incidence area of malignancies in China. Up to now, most of the studies on ST mainly involved in field of the detection method, mutagenic and carcinogenic assay. In the past a few years, studies in our lab had showed that Sterigmatocystin (ST) and deoxynivalenol (DON) are all predominant mycotoxins contaminated in foods, water and feed of cereal origin of local residents in the high incidence area of esopghageal, stomach and lung cancers in Hebei province. The previous experimental study also manifested that ST was carcinogenic to human fetal lung and gastric mucosal cells in vitro and mutagenic to human lymphocytes in vitro and murine lymphocytes in vivo. DON had been found to have immunosuppressive effects on both human and experimental animals. The results of animal experiments showed that mice fed with Aspergillus versicolor-inoculated corn flour could induce adenocarcinoma of the lung and atypical hyperplasia of the glandular stomach.Nevertheless, there were still some problems or doubts needed to comprehend deeply at present. Previous experiments on effects of ST mostly was carried out in vitro while the animal tumor induction experiments oncarcinogenesis of ST just using feeds contained Aspergillus versicolor culture, thus the results may not be exclusive enough because it is very difficult to eliminate the putative effects of other carcinogen that may present in the feeds used. As we all know that human body is an very complicated biological system, metabolic effects may affects the carcinogenicity of carcinogens. Meanwhile, the status of immune system also play important roles on the initiation and progression of cancer.To evaluate the adverse effects of ST on human, it is important and necessary to further elucidate the effects of ST on immune system and to verify exact effect of oral administration of ST on the carcinogenesis of lung and stomach in vivo. Aimed to try to find out more biological effects of ST on animal or human and to provide fuller data for ST carcinogenesis hypothesis as well as to explore the putative effects of sterigmatocystin (ST) on human help T lymphocyte (Thl) function, the following studies were carried out:1. The effects of ST on interleukin II (IL-2) and interferon- Y (IFN- y ) secretion of HPBMc were studied with ELISA method in vitro. 2.The effects of single exposure of ST on apoptosis and proliferation of hepatocytes, renal and gonadal cells in Kunming mice were evaluated with flow cytometric (FCM) analysis in vivo. 3.The toxic effects and carcinogenesis of long-term exposure of ST on NIH mice were carried out by animal experiment in vivo.As we know that mycotoxins contaminated to foodstuffs are usually mixed contamination, several mycotoxins could be detected in the same food sample. DON, which is reported no carcinogenic, is one of the predominating mycotoxins in the foodstuffs of high incidence area of malignancies in China. To further explore the bioeffects of ST, on the bases of the mycotoxin contamination of foodstuffs of our county, the effects of DON on ST were studied at the same time on the long-term experiment.Methods1 Determination of interleukin n (IL-2) and interferon- Y (IFN- Y )The levels of interleukin II (IL-2) and interferon- Y (IFN- Y ) of human peripheral blood mononuclear cells (HPBMc) in culture supernate were determined with enzyme-linked immunosorbent assay (ELISA) method at different dosage and different time point after ST treatment to explore its putative effects on human help T lymphocyte (Thl) function in vitro.2 Analysis of apoptosis and proliferationThe effects of ST on apoptosis and proliferation of hepatocytes, renal and gonadal cells of KM mice were quantitatively studied with flow cytometric (FCM)...