Abstract
The distribution of a single low dose of [3H]ochratoxin A (OTA) in different tissues of male Wistar rats, after administration by intubation, was investigated after 5 h, 24 h and 48 h. This dose corresponds to concentrations encountered in naturally contaminated feed (4 ppm). The distribution of [3H]-label varied with the time elapsed after administration; at 5 h the highest specific label was found in the stomach contents and in decreasing order in: intestinal contents, lung, liver, kidney, heart, fat, intestine, testes, and the lowest in muscles, spleen and brain. With exception of brain, fat, stomach and lung, all tissues showed maximum levels at 24 h, after which time the label decreased steadily, whereas in fat it increased.
After a 12-week feeding experiment, with doses of 288.8 μg/kg corresponding to an intake of 4 ppm in feed each 48 h, the DNA in liver and kidneys was investigated for damage. By the alkaline elution method combined with micro-spectrofluorimetric determinations of DNA, evidence for DNA single-strand breaks was obtained. These findings support reports on the carcinogenic action of OTA.
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References
Appelgreen LE, Arora RG (1983) Distribution of [14C]-labeled ochratoxin A in pregnant mice. Fd Chem Toxic 21: 563–568
Austwick PC (1981) Balkan nephropathy. The Practitioner 225: 1031–1038
Bendele SA, Carlton WW, Krogh P, Lillehoj EB (1983) Ochratoxin A carcinogenesis in the mouse. Abstracts of the 3rd Mycological Congress, Tokyo, p 21
Berndt WO, Hayes AW, Phillips RD (1980) Effects of mycotoxins on renal function. Mycotoxic nephropathy. Kidney International 18: 656–664
Bunge I, Heller K, Röschenthaler R (1979) Isolation and purification of ochratoxin A. Z Lebensm Unters Forsch 168: 457–458
Chang F, Chu FS (1977) The fate of ochratoxin A in rats. Food Cosmet Toxicol 15: 199–204
Creppy EE, Lorkowski G, Röschenthaler R, Dirheimer G (1982) Kinetics of immunosuppressive action of ochratoxin A in mice. In: Technical University Vienna (ed), Mycotoxins Phycotoxins, p 289
Creppy EE, Röschenthaler R, Dirheimer G (1984) Inhibition of protein synthesis in mice by ochratoxin A and its prevention by phenylalanine. Fd Chem Toxic 22: 883–886
Creppy EE, Størmer FC, Röschenthaler R, Dirheimer G (1983) Effects of two metabolites of ochratoxin A, (4R)-4-hydroxyochratoxin A and ochratoxin α on the immune response in mice. Infect Immun 39: 1015–1018
Elling F, Halb B, Jacobsen C, Krogh P (1975) Spontaneous toxic nephropathy in poultry associated with ochratoxin A. Acta Path Microbiol Scand Sect A 83: 739
Galtier P (1974) Devenir de l'ochratoxine A dans l'organisme animal. II Distribution tissulaire et élimination chez la rat. Ann Rech Vet 5: 319–328
Galtier P, Charpenteau JL, Alvinerie M, Labouche C (1979) The pharmacokinetic profile of ochratoxin A in the rat after oral and intravenous administration. Drug Metab Dispos 7: 429–434
Golinski P, Hult K, Grabarkiewicz-Szczesna J, Chelkowski J, Kneblewski P, Szebiotko K (1984) Mycotoxic porcine nephropathy and spontaneous occurrence of ochratoxin A residues in kidneys and blood of Polish swine. Appl Environ Microbiol 47: 1210–1212
Harwig J (1974) Ochratoxin A and related metabolites. In: IFH Purchase ed, Mycotoxins, Elsevier p 345
Haubeck HD, Lorkowski G, Kölsch E, Röschenthaler R (1981) Immunosuppression by ochratoxin A and its prevention by phenylalanine. Appl Environ Microbiol 41: 1040–1042
Hult K, Hokby E, Gatenbeck S, Rutqvist L (1980) Ochratoxin A in blood from slaughter pigs in Sweden: use in evaluation of toxin content of consumed feed. Appl Environ Microbiol 39: 828–830
Hult K, Plěstina R, Čeovic S, Habazin-Novak V, Radic B (1982) Ochratoxin A in human blood: Analytical results and confirmation tests from a study in connection with Balkan endemic nephropathy. In: Technical University Vienna (ed), Mycotoxins Phycotoxins, p 338
Imaida K, Hirose M, Ogiso T, Kurata Y, Ito N (1982) Quantitative analysis of initiating and promoting activities of five mycotoxins in liver carcinogenesis in rats. Cancer lett 16: 137–143
Kanisawa M (1983) Carcinogenicity of ochratoxin A and citrinin. Abstracts of the 3rd Mycological Congress Tokyo, p 136
Kanisawa M, Suzuki S (1978) Induction of renal and hepatic tumors in mice by ochratoxin A, a mycotoxin. Gann 69: 599–600
Kissane JM, Robins E (1958) The fluorimetric measurement of deoxyribonucleic acid in animal tissues with special reference to the central nervous system. J Biol Chem 233: 184–188
Kohn KW (1979) Measurement of macromolecular DNA damage produced in mammalian cells by anticancer agent and carcinogens. Methods in Cancer Research 16: 291–345
Krogh P (1974) Mycotoxic porcine nephropathy: a possible model for Balkan endemic nephopathy. In: Pachler, Dinev, Milev and Doichinov (eds) Endemic Nephropathy, Bulgarian Academy of Sciences, Sofia, p 266
Krogh P, Hald B, Petersen EJ (1973) Occurrence of ochratoxin A and citrinin in cereals associated with porcine nephropathy. Acta Path Microbiol Sand Sect B, 81: 689
Kumagai S, Kageaki A (1982) Intestinal absorption and secretion of ochratoxin A in the rat. Toxicol Appl Pharmacol 64: 94–102
Leistner L (1983) Toxigenic Penicillia occurring in feeds and foods. Abstracts of the 3rd Mycological Congress Tokyo, p 162
Leistner L, Pitt JI (1977) Miscellaneous Penicillium toxins. In: JV Rodricks, CW Hesseltine, Mehlman MA (ed), Mycotoxins in human and animal health, Pathotox Publishers Inc. Park Forest South, Illinois p 639
Lillehoj EB, Kwolek WF, Elling F, Krogh P (1979) Tissue distribution of radioactivity from ochratoxin A-14C in rats. Mycopathologia 68: 175–177
Prior MG, Sisodia CS (1982) The effects of ochratoxin A on the immune response of swiss mice. Can J Comp Med 46: 91
Scott PM, Walbeck W, Kennedy B, Anyeti D (1972) Mycotoxins (ochratoxin A, citrinin and sterigmatocystin) and toxigenic fungi in grains and other agricultural products. Mycotoxins and Toxigenic Fungi 20: 1103–1105
Suzuki S, Satoh T, Yamazaki M (1977) The pharmacokinetics of ochratoxin A in rats. Jpn J Pharmacol 27: 735–744
Szafarz D (1977) An improved method for DNA alkaline gradient analysis and its application to the effect of carcinogens on mouse liver DNA. Biochimie 59: 775–776
Szczech GM, Hood RD (1981) Brain necrosis in mouse fetuses transplantally exposed to the mycotoxin ochratoxin A. Toxicol Appl Pharmacol 57: 127–137
Ueno Y, Kubota K (1976) DNA-attacking ability of carcinogenic mycotoxins in recombinaison-deficient mutant cells of Bacillus subtilis sporulation by ochratoxin A. FEMS Microbiol Lett 4: 147
Umeda M, Tsutsui T, Saito M (1977) Mutagenicity and inductibility of DNA single-strand breaks chromosome aberrations by various mycotoxins. Gann 68: 619–625
Wehner FC, Thiel PG, Van Rensburg SJ, Demasius IPC (1978) Mutagenicity to Salmonella typhimuriums of some Aspergillus and Penicillium mycotoxins. Mutat Res 58: 193–203
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Kane, A., Ekué Creppy, E., Roth, A. et al. Distribution of the [3H]-label from low doses of radioactive ochratoxin a ingested by rats, and evidence for DNA single-strand breaks caused in liver and kidneys. Arch Toxicol 58, 219–224 (1986). https://doi.org/10.1007/BF00297109
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DOI: https://doi.org/10.1007/BF00297109