- Email: [email protected]
‘Unicorn’ among rats exposed to mycotoxins from Fusarium
Toxicology Letters, 16 (1983) 211-215 Elsevier
‘UNICORN’
AMONG
RATS EXPOSED
211
TO MYCOTOXINS
FROM
FUSARIUM (T-2 toxin; zearalenone;
squamous carcinoma)
R. SCHOENTAL Department of Pathology, Royal Veterinary College, University of London, Royal College Street, London NW1 OTU (U.K.) (Received August 3rd, 1982) (Accepted October 27th, 1982)
SUMMARY A horn-like nodule developed in the middle of the forehead of a white rat, exposed perinatally to T-2 toxin and to zearalenone, the secondary metabolites of Fusarium. The hard nodule consisted mainly of keratine, derived from a squamous carcinoma spreading through the nasal turbinals and invading the brain.
Mythological representation of creatures with abnormal organs previously considered as fictional, might have been based on observations of rare abnormalities caused by environmental teratogens or carcinogens derived from plants or microorganisms. Cyclopian single eye in the middle of the forehead have been observed among offspring of sheep, when these consumed the plant Veratrum cafifornicum (Durand) Liliaceae (false hellebore), during the 14th day of pregnancy [l]. The alkaloidal constituents of this plant [2], especially cyclopamine (iso-deoxojervine), have been shown to reproduce such cyclopian-type lesions [3]. The mythological ‘unicorn’ might have also been based on factual observations. References to such wild animals are included in the Bible [4]. In the course of experiments, in which rats were exposed to mycotoxins from Fusarium microfungi, the irritant T-2 toxin and the oestrogenic zearalenone, a male white rat developed a horn-like nodule in the middle of his forehead. The rat was killed when appearing in poor condition at 21.5 months of age. At post mortem the rat had also abnormalities of its testes: the right one was atrophic, the left one was 0378-4274/83/$03.00 0 Elsevier Science Publishers B.V.
212
enlarged due to the presence of an interstitial cell tumour. Microscopic examination of sections from the decalcified head shows that the horn-like nodule is composed of keratin, derived from a highly keratinizing squamous carcinoma, which spread through the nasal turbinals (Figs. 1 and 2) and formed metastases in the brain (Fig. 3).
Fig. 1. Section through the forehead of a male rat, killed when 21.5 months old, showing masses of keratin surrounded by squamous carcinoma. The rat was from a third litter of a female, which had 3 daily skin apphcations of T-2 toxin (1 mg/ml in ethyl acetate) before being mated 3 weeks later to an untreated male, and about 16 weeks before the birth of this rat. At 3 days of age the young rat was injected i.p. with zearalenone (0.5 mg10.02 ml of 20% aq.ethanol). Haematoxyiin and eosin x 50.
213
Fig. 2. Section through the nasal turbinals of the rat shown in Fig. 1. Note a sm14 tumour nodule in the centre. H & E x 50.
Such forehead tumours have not been seen in previous experimen Its in which white rats were treated with several large doses of T-2 toxin [5], nor in more recent experiments in which zearalenone was used alone, or in conjunctior 1 with T-2 toxin; turnours, benign and malignant, of sex organs, including the testes, have been found in the treated rats. Very high levels of mycotoxins may occasionally be present in dec:aying vegetation under exceptional weather conditions, and affect wild (and other) animals exposed to the mycotoxins perinatally.
214
Fig. 3. Metastatic nodules in the brain of the rat shown in Fig. 1. H & E x 50.
ACKNOWLEDGEMENTS
I am indebted to Professor E. Cotchin for hospitality in his Department and to the MRC for financial support. I thank Mr. Martin Robins for the sections, Mr. R.F. Legg for the photomicrographs, and Miss S. Spencer for the excellent care of the animals. REFERENCES 1 W.A. Binns, L.F. James, J.L. Shupe and G.A. Everett, Congenital cyclopian-type malformation in lambs induced by maternal ingestion of a range plant, Verutrum culifornicum, Am. J. Vet. Res., 24 (1%3) 1164-1175.
215 2 R.F. Keeler and W.A. Binns, Teratogenic compounds of Veratrum californicum (Durand), V. Comparison of cyclopian effects of steroidal alkaloids from the plant and structurally related compounds from other sources, Teratology, 1 (1968) S-10. 3 R.F. Keeler, Teratogenic compounds of Veratrum californicum (Durand), VI. The structure of cyclopamine, Phytochemistry, 8 (1969) 223-225. 4 The holy Bible, Job 39: 9-12. 5 R. Schoental, A.Z. Joffe and B. Yagen, Cardiovascular lesions and various tumors found in rats given T-2 toxin, a trichothecene metabolite of Fusurium species, Cancer Res., 39 (1979) 2179-2189.
‘UNICORN’
AMONG
RATS EXPOSED
211
TO MYCOTOXINS
FROM
FUSARIUM (T-2 toxin; zearalenone;
squamous carcinoma)
R. SCHOENTAL Department of Pathology, Royal Veterinary College, University of London, Royal College Street, London NW1 OTU (U.K.) (Received August 3rd, 1982) (Accepted October 27th, 1982)
SUMMARY A horn-like nodule developed in the middle of the forehead of a white rat, exposed perinatally to T-2 toxin and to zearalenone, the secondary metabolites of Fusarium. The hard nodule consisted mainly of keratine, derived from a squamous carcinoma spreading through the nasal turbinals and invading the brain.
Mythological representation of creatures with abnormal organs previously considered as fictional, might have been based on observations of rare abnormalities caused by environmental teratogens or carcinogens derived from plants or microorganisms. Cyclopian single eye in the middle of the forehead have been observed among offspring of sheep, when these consumed the plant Veratrum cafifornicum (Durand) Liliaceae (false hellebore), during the 14th day of pregnancy [l]. The alkaloidal constituents of this plant [2], especially cyclopamine (iso-deoxojervine), have been shown to reproduce such cyclopian-type lesions [3]. The mythological ‘unicorn’ might have also been based on factual observations. References to such wild animals are included in the Bible [4]. In the course of experiments, in which rats were exposed to mycotoxins from Fusarium microfungi, the irritant T-2 toxin and the oestrogenic zearalenone, a male white rat developed a horn-like nodule in the middle of his forehead. The rat was killed when appearing in poor condition at 21.5 months of age. At post mortem the rat had also abnormalities of its testes: the right one was atrophic, the left one was 0378-4274/83/$03.00 0 Elsevier Science Publishers B.V.
212
enlarged due to the presence of an interstitial cell tumour. Microscopic examination of sections from the decalcified head shows that the horn-like nodule is composed of keratin, derived from a highly keratinizing squamous carcinoma, which spread through the nasal turbinals (Figs. 1 and 2) and formed metastases in the brain (Fig. 3).
Fig. 1. Section through the forehead of a male rat, killed when 21.5 months old, showing masses of keratin surrounded by squamous carcinoma. The rat was from a third litter of a female, which had 3 daily skin apphcations of T-2 toxin (1 mg/ml in ethyl acetate) before being mated 3 weeks later to an untreated male, and about 16 weeks before the birth of this rat. At 3 days of age the young rat was injected i.p. with zearalenone (0.5 mg10.02 ml of 20% aq.ethanol). Haematoxyiin and eosin x 50.
213
Fig. 2. Section through the nasal turbinals of the rat shown in Fig. 1. Note a sm14 tumour nodule in the centre. H & E x 50.
Such forehead tumours have not been seen in previous experimen Its in which white rats were treated with several large doses of T-2 toxin [5], nor in more recent experiments in which zearalenone was used alone, or in conjunctior 1 with T-2 toxin; turnours, benign and malignant, of sex organs, including the testes, have been found in the treated rats. Very high levels of mycotoxins may occasionally be present in dec:aying vegetation under exceptional weather conditions, and affect wild (and other) animals exposed to the mycotoxins perinatally.
214
Fig. 3. Metastatic nodules in the brain of the rat shown in Fig. 1. H & E x 50.
ACKNOWLEDGEMENTS
I am indebted to Professor E. Cotchin for hospitality in his Department and to the MRC for financial support. I thank Mr. Martin Robins for the sections, Mr. R.F. Legg for the photomicrographs, and Miss S. Spencer for the excellent care of the animals. REFERENCES 1 W.A. Binns, L.F. James, J.L. Shupe and G.A. Everett, Congenital cyclopian-type malformation in lambs induced by maternal ingestion of a range plant, Verutrum culifornicum, Am. J. Vet. Res., 24 (1%3) 1164-1175.
215 2 R.F. Keeler and W.A. Binns, Teratogenic compounds of Veratrum californicum (Durand), V. Comparison of cyclopian effects of steroidal alkaloids from the plant and structurally related compounds from other sources, Teratology, 1 (1968) S-10. 3 R.F. Keeler, Teratogenic compounds of Veratrum californicum (Durand), VI. The structure of cyclopamine, Phytochemistry, 8 (1969) 223-225. 4 The holy Bible, Job 39: 9-12. 5 R. Schoental, A.Z. Joffe and B. Yagen, Cardiovascular lesions and various tumors found in rats given T-2 toxin, a trichothecene metabolite of Fusurium species, Cancer Res., 39 (1979) 2179-2189.