Aflatoxin, a metabolic product of Aspergillus flavus and A, parasiticus, is one of the strongest carcinogenic compounds, and it is found in several kinds of foods and foodstuffs. Most countries set limits on aflatoxins, and the regulation level in Japan is 10 ppb for aflatoxin B1. In our laboratory, aflatoxins in foods and foodstuffs have been tested since 1971, when aflatoxin was first found in peanut cream in Japan. This report summarizes the data on aflatoxin contamination in commercial foods and foodstuffs in Tokyo for 15 years during the period of 1982-1996.
Deoxynivalenol (DON) and nivalenol (NIV) are trichothecene mycotoxins produced princi-pally by Fusarium graminearum Schwabe (telemorph Gibberella zeae (Schw.) Petch.), one of the major pathogenic fungi of head blight diseases in wheat and barley and rot in corn. They occur worldwide in these plant products intended for human and animal consumption, causing the economical loss and the health risk in humans and animals. In Japan, DON and NIV are recognized as two major trichothecenes coincidentally occurring in domestic wheat and barley grains. As for the mechanism of the epidemic of head blight disease and mycotoxin occurrence in wheat and barley, the following sequential steps are involved : i) the production of G. zeae perithecia on plant debris, like overwintered rice-stubbles, ii) the aerial ascospores dispersal from perithecia to infection sites (spikes), iii) the infection at anthesis and the clonization in spikes under the suitable moisture and temperature conditions, and iv) the fungal growth and the accumulation of mycotoxins in the process of head maturation. Although several papers have suggested the geographic difference in relation to the occurrence of trichothecenes in Japanese wheat and barley, there are only few reports studying the above steps systematically. Recently, we have attempted comprehensive chemical and mycological studies on the features of the occurrence of trichothecenes in Japan. This paper reviews the characteristics of natural occurrence of DON and NIV in Japanese wheat and barley.
We studied that the effect of relatively low doses of five trichothecens (deoxynivalenol (DON), diacetoxyscirpenol (DAS), T-2 toxin (T-2), fusarenon-X (FX) and nivalenol (NlV)) on the host resistance against Salmonella infection using mice. Mice given daily each trichothecene in drinking water were infected orally with Salmonella enteritidis 14 days after the commencement of exposure to trichothecens. It was found that DON was most effective among five trichothecene derivatives in decreasing the resistance against Salmonella infection. This effect of DON was associated with the reduction of serum anti-Salmonella 1 gM titer and delated type hypersensitivety reaction, both of which are regarded as defense mechanisms against Salmonella infection. These results suggest that dietary exposure to low doses of DON enhances the susceptibity to oral infection to Salmonella through toxic effects on cellular and humoral immunity.
Employing a competitive ELISA (cELISA) based on monoclonal antibody (MAb) and an immunoaffinity-column (IAC)-linked HPLC-fluorometry, ochratoxin A (OTA) levels in the plasma of 184 healthy volunteers (130 males, 54 females) and the beverages including wine, beer, coffee, grape juice, spirits and soy-sauce (138 samples in total) were surveyed in Tokyo. It was found that 85% of the total human plasma sampled in 1992, 1994, 1995 and 1996 were positive for OTA except 38% in 1994, and an average value in the positives was estimated to 68 pg/ml. This suggests that the population in Tokyo is exposed to OTA at high frequency, though the level in plasma is far less than that reported in Europe and Canada. Alcoholic drinks such red wine and beer, coffee products and soy-sauce were positive for OTA. A partial contribution of these alcoholic drinks, coffee and soy-sauce is suspected as the source of the OTA observed in the human plasma.
Emodin (EM) is an anthoraquinoid mycotoxin and a component of medicinal plants, and 2-hydroxy-emodin (2-OH-EM) is one of the active metabolites of EM. Effects of 2-OH-EM and EM on the activation of 2-amino-3-methyl-imidazo [4, 5-f] quinoline (IQ) was evaluated using a Salmonella - microsome system (Ames test) in the presence of 7, 8-benzoflavone (BF), an inhibitor of hepatic cytochrome P-4501A. Using the Ames test with the Salmonella Typhimur-ium strain TA98 (TA98), 2-OH-EM and EM almost completely inhibited the mutagenicity of IQ (4 ng/plate) at 5μg and 1μg/plate, with IC50 values of 3.0 and 0.7μg/plate, respectively. With the S. Typhimurium strain TA1537 (TA1537), no decrease of IQ-induced revertant numbers was observed for either 2-OH-EM or EM. While IQ showed no effect on the mutagenicity of 2-OH-EM, it reduced the mutagenic activity of EM by 50%. These data suggest that the anti-mutagenic effect of EM and its metabolite can be attributed to the competitive inhibition of the microsomal activation of IQ. The present study showed for the first time the antimutagenic activity of 2-OH-EM against cooked-food mutagens in TA98 and TA1537 with S9 mix.
T-2 toxin, a mycotoxin produced by fungi Fusarium spp., is a potent inducer of apoptosis in human promyelotic lymphoma cell line HL-60, peripheral blood lymphocytes (PBLs) and several tissues such as thymus, spleen and liver of mice. We have previously reported that intracellular calcium ion levels play a critical role in T-2 toxin-induced apoptosis. In this research, to clarify the signal transduction pathway of T-2 toxin-induced apoptosis, we inves-tigated whether the activation of ICE family proteases (caspases) and the disruption of mitochondrial transmembrane potential (Δψm) are provoked by T-2 toxin. The activation of caspase-3, not caspase-1, was confirmed within 90 min after exposure to 100 ng/ml of T-2 toxin. Furthermore, a low concentration (6 ng/ml) of T-2 toxin-induced apoptosis was blocked by pretreating with caspase-3 inhibitor, Ac-DEVD-CHO. The disruption of Δψm was provoked within 30 to 60 min. These results indicate that the apoptotic cascade primed by T-2 toxin is mediated by a common cascade of apoptosis which is recognized in Fas and several anticancer agents.