Abstract
Patulin (PAT), a highly toxic, carcinogenic, heterocyclic lactone is produced by a variety of fungal species, including Penicillium and Aspergillus. This compound has been isolated from various apple products and is stable in apple and grape juice and dry corn. It has been reported to be cytotoxic and to exert adverse influence on development in vivo in mice and merits further study and evaluation. In this study, whole rate embryo culture (WEC) was used to determine the teratogenic potential of PAT in vitro. Embryos were exposed to PAT-treated (0.00–62 μM) rat serum for 45 h. The embryos that were exposed to 62 μM PAT were not evaluated because they did not survive beyond 40 h of incubation. The results indicate that PAT induced a statistically significant reduction in protein and DNA content, yolk sac diameter, crown rump length, and somite number count. Patulin treatment also resulted in an increase in the frequency of defective embryos. Anomalies included growth retardation, hypoplasia of the mesencephalon and telencephalon, and hyperplasia and/or blisters of the mandibular process. Thus, the data from the present study provide further evidence supporting the conclusion that the whole rat embryo assay is a rapid and sensitive in vitro method that can be employed to pre-screen developmentally toxic mycotoxins.
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References
Arafat W, Kern D, Dirheimer G (1985) Inhibition of aminoacyl-tRNA synthetases by the mycotoxin patulin. Chem Biol Interact 56:333–349
Ashoor SH, Chu FS (1973) Inhibition of muscle aldolase by penicillic acid and patulin in vitro. Food Cosmet Toxicol 11:995–1000
Bradford M (1976) A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254
Burghardt RC, Barhoumi R, Lewis EH, Bailey RH, Pyle KA, Clements BA, Phillips TD (1992) Patulin-induced cellular toxicity: A vital fluorescence study. Toxicol Appl Pharmacol 112:235–244
Ciegler A (1977) Patulin. In: Rodricks JV, Hesseltine CW, Mehlman MA (eds) Mycotoxins in human and animals health. Pathotox, Park Forest South, IL, pp 609–624
Ciegler A, Beckwith SC, Jackson LK (1976) Teratogenicity of patulin and patulin adducts formed with cysteine. Appl Environ Microbiol 32:664–667
Dalton JE (1952) Keliod resulting from a positive patch test. AMA Arch Dermatol Syphilol 65:53
Dryden CJ, Mayura K, Clements BA, Becker M, Phillips TD (1991) Evaluation of the developmental toxicity of cyclopiazonic acid using Hydra attenuata and postimplantation rat whole embryo bio-assay. Toxicol Abstr 11:296
Friedman L (1990) Patulin-mycotoxin or fungal metabolite? (Current state of knowledge). In: Llewellyn G, O'Rear C (eds) Biodeterioration research III. Plenum, NY, pp 24–51
Hayes AW (1981) Mycotoxin teratogenicity and mutagenicity. CRC Press Inc, Boca Raton, FL
Kahn JB Jr (1957) Effects of various lactones and related compounds on cation transfer in incubated cold stored human erythrocytes. J Pharmacol Exp Ther 121:234
Kitchin KT, Schmid BP, Sanyal MK (1986) Rodent whole embryo culture as a teratogen screening method. Methods Find Exp Clin Pharmacol 8:291–301
Korzybski T (1967) Patulin, syn. clavicin, clavatin, claviformin, expansin penicidin. In: Gottlibe D, Shaw PD (eds) Antibiotics: Mechanism of action. Vol 1 Springer-Verlag, NY, pp 1223–1230
Labarca C, Paigen K (1980) A simple, rapid, and sensitive DNA assay procedure. Anal Biochem 102:344–352
Lee KS, Roschenthaler R (1987) Strand scissions of DNA by patulin in the presence of reducing agents and cupric ions. J Antibiot 40:692–696
Lindroth S, von Wright A, (1990) Detoxification of patulin by adduct formation with cysteine. J Environ Pathol Toxicol Oncol 10:254–259
Mayura K, Edwards JF, Maull EA, Phillips TD (1989) The effects of ochratoxin A on postimplantation rat embryos in culture. Arch Environ Contam Toxicol 117:411–415
Moule Y, Hatey F (1977) Mechanism of the in vitro inhibition of transcription by patulin, a mycotoxin from Byssochlamys nivea. FEBS Lett 74:121–125
New D (1978) Whole-embryo culture and the study of mammalian embryos during organogenesis. Biol Rev 53:81–122
Ott L (1988) An introduction to statistical methods and data analysis. PMS-Kent Publ Co, Boston, pp 451–455
Phillips TD, Hayes W (1978) Effects of patulin on the kinetics of substrate and cationic ligand activation of adenosine triphosphatase in mouse brain. J Pharmacol Exp Ther 205:606–616
—, — (1977) Effects of patulin adenosine triphosphatase activities in the mouse. Toxicol Appl Pharmacol 42:175–187
Reiss J (1975) Mycotoxin poisoning of Allium cepa root tips II. Reduction of mitotic index and formation of chromosomal aberrations and cytological abnormalities by patulin, rubratoxin B and diacetoxyscirpenol. Cytologia 40:703
Riley RT, Showker JL (1991) The mechanism of Patulin's cytotoxicity and the antioxidant activity of indole tetramic acids. Toxicol Appl Pharmacol 109:108–126
Roll R, Matthiaschk G, Korte A (1990) Embryotoxicity and mutagenicity of mycotoxins. J Environ Pathol Toxicol Oncol 10:1–7
SAS Institute, Inc (1985) SAS/SAT Guide for personal computers. SAS Institute, Cary, NC
Schmid BP, Goulding E, Kitchin K, Sanyal MK (1981) Assessment of the teratogenic potential of acrolein and cyclophosphamide in a rat embryo culture system. Toxicology 22:235–243
Schmid BP, Cicurel L (1986) Application of the post-implantation rat embryo culture system to in vitro teratogenicity testing. Food Chem Toxicol 24:623–626
Scott PM (1974) Patulin. In: Purchase IFH (ed) Mycotoxins. Elsevier, NY, pp 383–403
Singh J (1967) Patulin. In: Gottlieb D, Shaw PD (eds) Antibiotics. Springer-Verlag, NY, p 621
Small MH, Smith EE, Braithwaite CE, Duffus E, Phillips T, Reine A (1991) Evaluation of the developmental toxicity of ochratoxin A and cyclopiazonic acid in postimplantation rat embryo. Toxicol Abstr 11:297
Stott WT, Bullerman LB (1975) Patulin: A mycotoxin of potential concern in foods. J Milk Food Technol 38:695–705
Ueno T, Matsumoto H, Ishii K, Kukita KI (1976). Inhibitory effects of mycotoxins on Na+-dependent transport of glycine in rabbit reticulocytes. Biochem Pharmacol 25:2091–2095
Umeda M, Yamamoto T, Saito M (1972) DNA-strand breakage of Hela cells induced by several mycotoxins. Jpn J Exp Med 42:527
Wilson DM (1976) Patulin and penicillic acid. In: Rodricks JV (ed) Mycotoxins and other fungal related food problems, Adv Chem Ser 149. Am Chem Soc, Washington, DC, pp 90–109
Yang YG, Mayura K, Phillips TD (1990) Evaluation of the developmental toxicity of citrinin using Hydra attenuata and postimplantation rat whole embryo culture. Toxicol Abstr 10:273
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Smith, E.E., Duffus, E.A. & Small, M.H. Effects of patulin on postimplantation rat embryos. Arch. Environ. Contam. Toxicol. 25, 267–270 (1993). https://doi.org/10.1007/BF00212140
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DOI: https://doi.org/10.1007/BF00212140