Acute toxicity in the microbial poisonings plays an important role not only in occurrence of such poisonings in the field but also in detections and purification of the toxins in laboratories. Factors associated with acute toxicities are as toxin solubility, absorption by the body, administration route, potency, interval between intake and onset of poisoning symptoms, and toxin target. Characteristics of the acute toxicities induced by several mycotoxins and phycotoxins areanalyzed and discussed.

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アフラトキシンB₁(AFB₁)は強い肝毒性とともに発癌性を有しており,諸種実験動物に肝癌を引き起こすことが明かにされている.また,近年AFB₁の高汚染地域である東南アジアやアフリカにおいてAFB₁汚染食品の摂取量とヒト肝細胞癌(HCC)の発生頻度の間には明らかな相関性が認められること,およびこれら地域のHCCで癌抑制遺伝子P53の249番目のコドンAGG(Arg)がAGT(Ser)に50%もの高率で変異していることが報告されている.これらのことより,AFB₁はB型肝炎ウイルスとともにヒト肝癌発生の原因物質の一つとして考えられている.しかし,AFB₁の詳細な発癌メカニズムに関しては不明な点が多い.そこで我々はAFB₁誘発ラット肝癌より2種類の細胞株(Kagura-1とKagura-2)を樹立し,これら細胞の諸性質を解析する過程で神経分化誘導因子が産生されていることを見出した.本論文ではKagura-1とKagura-2細胞の特性とこれらの細胞が産生する神経分化誘導因子について概説する.

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1987年,千葉大学真核微生物研究センターが発足したのを機に,我々は,それまで行ってきたアゾ色素発がんの研究を土台として,真核微生物トキシンの中で最も発がん作用が強く,かつ,研究の進んでいるテフラトキシンB₁(AFB₁)についてラット肝臓の発がん,肝がん細胞の細胞生物学をテーマとして研究を開始した.当研究センターは,全国共同利用施設として内外の研究者の協力を得て真核微生物に関する研究を進めているが,これまで,国立がんセンターの児玉昌彦博士により,AFB₁がラット肝臓酵素により代謝されてフリーラジカルを形成してDNAと結合することが,また,チェコスロヴァキアのツクローバ博士により,AFB₁が骨髄造血前駆細胞の顆粒球への成熟と免疫細胞によるサイトカィンの産生を阻害することが明らかにされた.本シンポジゥムにおいては,AFB₁の毒性軽減,並びに,AFB₁誘発肝がん組織からの転移性細胞株の分離について述べるが,この研究は麻布大の岸川正剛博士との共同研究として進めてきたものである.

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Some species of the genus Penicillium (P. palitans, P. expansum and P. farinosum) were examined for the ability to produce nitrogen-containing mycotoxins (alkaloids) on synthetic, complex media, summer wheat and apple juice in the submerged and surface culture. Bioproduction of clavine and benzodiazepine alkaloids was observed in all media tested in surface conditions. However, the essential differences were found in the total amounts of alkaloids as well as in the ratio of separate components and their distribution between the mycelium and culture broth. It was suggested that a correlation exists between the ability of fungi to produce N-containing mycotoxins (alkaloids) on artificial media and that on natural substrates.

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Stimulatory effect of dimethyl sulfoxide (DMSO) on trichothecene biosynthesis by Fusarium graminearum KU 1352 [deoxynivalenol (DON) producer] and F. graminearum KU 1383 [nivalenol (NIV) producer)] were investigated in yeast extract-polypepton-sucrose medium. DMSO at concentrations subinhibitory to fungal growth significantly enhanced production of trichothecenes in both strains. Maximum yields of trichothecenes were 162% (660 μg/ml) of control at 5% DMSO in the DON producer and 141% (778 μg/ml) at 2% DMSO in the NIV producer. This is the first report on the enhancement of tricho-thecene production by DMSO without inhibition of biomass formation.

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Twenty-seven strains of Aspergillus niger group stored in the Institute for Fermenta-tion, Osaka (IFO) were examined for their ochratoxin A (OTA) producibility. TLC and HPLC analyses revealed the production of OTA by 5 out of the 27 strains, A. awamori var. fumeus IFO 4122, A. usamii IFO 8875, 8876, 8877, and A. usamii mut. shirousamii IFO 6082. The production was also confirmed by its spectral assignment of both nuclear magnetic resonance (NMR) and mass spectra (MS).

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Trichothecium roseum causes pink mold rot of muskmelons and tomatoes cultivated in greenhouses, and also produces trichothecin, a 12, 13-epoxytrichothecene. To clarify the pathogenicity and trichothecin production of T. roseum, mycological examination was carried out in 8 greenhouses in Chiba Prefecture. The contamination of muskmelon and tomato fruits with trichothecin was also examined. Trichothecium roseum was isolated from almost all of the moldy or discolored muskmelon and tomato fruits, as well as tomato stem dumped near the greenhouse. The fungus was found in the air of a greenhouse in which many moldy tomato fruits were present, but in none of the soil samples from the greenhouses tested. In an inoculation test, T. roseum isolated from muskmelon and tomato invaded and decayed the flesh of matured muskmelons. Moreover, almost all the isolates of T. roseum tested produced trichothecin on Czapek-Dox broth supplemented with 0.2% corn steep liquor cultured for 21 days at 25°C. Trichothecin was detected in moldy muskmelon and tomato fruits collected in the greenhouses.

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Three new components, tentatively named GP-A, -B, and -C, with monoamine oxidase (MAO) inhibitory activity and a known anthraquinone chrysophanol were isolatedfrom Mycelia Sterilia derived from an Ascomycete, Gelasinospora pseudoreticulata.GP-A and -B, the main MAO inhibitory principles of this fungus, were deduced tobe 5-hydroxy-7-methoxy-4, 9-dioxonaphtho[2, 3-c]furan and l, 3-dihydro-5-hydroxy-7-methoxy-4, 9-dioxo-naphtho[2, 3-c]furan, respectively. The IC₅₀ values of GP-A, -B, and -C were evaluated against the MAO from mouse liver.

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Natural occurrences of aflatoxin B₁, fumonisins and trichothecenes were investigated in 80 corn samples harvested in the low and high risk of primary liver cancer, Penlai (Sandong) and Haimen (Jiangsu), respectively, in China in1993. In Haimen area, the positives were 37 (average levels of 24.0 ppb), 37 (average levels of 5.11 ppm), 25 (average levels of 2.02 ppm), 25 (average levels of 1.12 ppm) and 40 (average levels of 0.89 ppm) for aflatoxin B₁, fumonisins B₁, B₂, B₃ and deoxynivalenol, respectively. In Penlai area, 12, 2, and 9 out of 13 kernel samples were positive for aflatoxin B₁, fumonisin B₁ and deoxynivalenol, respectively. However, no fumonisin B₂ and B₃ were found in these Penlai's samples. As for other trichothecenes, nivalenol was detected in only one sample from Haimen, but no T-2 toxin was found in all corn samples in this investigation. These results indicate that co-contamination of aflatoxin B₁, fumonisins and deoxynivalenol is popular in Chinese corn. Furthermore, the positive rate for natural occurrence of combinated aflatoxin B₁ and fumonisins in Haimen was superior to those in Penlai. These results suggest that tumor risk factor in high frequency area of primary liver cancer in China may be associated with co-contamination of aflatoxin B₁ and fumonisins.

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