Induction of characteristic chromosomal aberrations, particularly X-trisomy, in cultured human lymphocytes treated by ochratoxin A, A mycotoxin implicated in Balkan endemic nephropathy

Manolova, Yanka; Manolov, G; Parvanova, L.; Petkova-Bocharova, T.; Castegnaro, M.; Chernozemsky, I. N.

doi:10.1016/0027-5107(90)90021-u

Cited by 34 publications

(12 citation statements)

References 13 publications

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“…The results of in vitro studies that have assessed the potential for OTA to cause DNA single-strand breaks, or other cytogenetic effects in mammalian cell lines are mixed, with both positive (Mori et al, 1984; Creppy et al, 1985; Štětina and Votava, 1986; Manolova et al, 1990; Ehrlich et al, 2002; Ali et al, 2010) and negative results (Cooray, 1984; Bendele et al, 1985; Štětina and Votava, 1986; NTP, 1989) reported. Variable results have been reported in the comet assays using in vitro exposures (Ehrlich et al, 2002; Lebrun et al, 2006; Simaro-Doorten et al, 2006; Arbillaga et al, 2007; Klaric et al, 2010).…”

Section: Genotoxicity Of Otamentioning

confidence: 99%

A reassessment of risk associated with dietary intake of ochratoxin A based on a lifetime exposure model

Haighton

Lynch

Magnuson

et al. 2012

Critical Reviews in Toxicology

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Mycotoxins, such as ochratoxin A (OTA), can occur from fungal growth on foods. OTA is considered a possible risk factor for adverse renal effects in humans based on renal tumors in male rats. For risk mitigation. Health Canada proposed maximum limits (MLs) for OTA based largely on a comparative risk assessment conducted by Health Canada (Kuiper-Goodman et al., 2010), in which analytical data of OTA in foods were used to determine the possible impact adopting MLs may have on OTA risks. The EU MLs were used for comparison and resultant risk was determined based on age–sex strata groups. These data were reevaluated here to determine comparative risk on a lifetime basis instead of age strata. Also, as there is scientific disagreement over the mechanism of OTA-induced renal tumors, mechanistic data were revisited. On a lifetime basis, risks associated with dietary exposure were found to be negligible, even without MLs, with dietary exposures to OTA three to four orders of magnitude below the pivotal animal LOAEL and the TD05. Our review of the mechanistic data supported a threshold-based mechanism as the most plausible. In particular, OTA was negative in genotoxicity assays with the highest specificity and levels of DNA adducts were very low and not typical of genotoxic carcinogens. In conclusion, OTA exposures from Canadian foods do not present a significant cancer risk.

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Section: Genotoxicity Of Otamentioning

confidence: 99%

A reassessment of risk associated with dietary intake of ochratoxin A based on a lifetime exposure model

Haighton

Lynch

Magnuson

et al. 2012

Critical Reviews in Toxicology

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“…(2) Manolova et al (1990) demonstrated the presence of chromosomal aberrations on chromosome X from human lymphocytes cultivated in the presence of OTA. Similar aberrations have been detected in BEN patients (Manolov et al 1991).…”

Section: Genotoxicity and Mutagenicitymentioning

confidence: 99%

Balkan endemic nephropathy and associated urinary tract tumours: a review on aetiological causes and the potential role of mycotoxins

Pfohl‐Leszkowicz

Petkova-Bocharova²,

In³

et al. 2002

Food Additives and Contaminants

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311

172

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A series of publications in the 1950s described a kidney disease in Bulgaria, the former Yugoslavia and Romania that became known as Balkan endemic nephropathy (BEN). The disease was qualified by World Health Organisation (WHO) experts as 'progressive and very gradually developing renal failure with insidious onset.... The last stage shows marked fibrosis...'. BEN is characterized by tubular degeneration, interstitial fibrosis and hyalinization of glomeruli accompanied by enzymuria and impaired renal function without nephrotic syndrome. Later, an association between BEN and tumours of the kidney pelvis and ureter was recognized, so that the problem of BEN became not only nephrological, but also oncological. There may also be an association with increased urinary bladder cancer incidence, although many confounding factors may interfere in the analysis of data for this organ. In view of the very intimate association between BEN and the urinary tract tumours (UTT), the term 'endemic uropathy' has been proposed. Several hypothesis concerning the aetiology of these diseases has been investigated, which include: predisposing genes factors, environmental factors (heavy metals, minerals, bacteria, leptospira, viruses, fungal toxins and, most recently, pliocene lignites). This paper reviews the different hypotheses about the aetiology of endemic uropathy and pays particular attention to the role of fungal toxins.

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“…Antioxidants were shown to prevent OTA-mediated increases in MDA production in vitro (Baudrimont et al 1997) and in vivo (Meki and Hussein 2001). In rats, the injection of superoxide dismutase and catalase provided protection against OTA-induced nephrotoxicity in vivo (Baudrimont et al 1994), and in mice, antioxidant vitamins reduced an OTAmediated increase in chromosomal aberrations (Manolova et al 1990) and the formation of 32 P-postlabelling spots (Grosse et al 1997). Several potential relevant oxido-reduction mechanisms have been identified and proposed.…”

Section: Oxidative Stressmentioning

confidence: 99%

Ochratoxin A: Potential epigenetic mechanisms of toxicity and carcinogenicity

Schilter

Marin-Kuan

Delatour

et al. 2005

Food Additives & Contaminants

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Assessment of the significance to human health of ochratoxin A (OTA) in food is limited by a lack of human toxicity data. Therefore, OTA risk evaluation relies mainly on the use of animal data, with renal carcinogenicity in rat being considered as the pivotal effect. The elucidation of the mechanism of action would improve the use of the carcinogenicity data for risk assessment. Direct genotoxicity versus epigenetic mechanisms appears to be a key question. In this presentation, new biochemical and toxicogenomic results obtained in a recent European project (EU-Grant # QLK1-CT-2001-011614) will be summarized in the context of previously reported mechanisms of action including inhibition of protein synthesis, production of oxidative stress and alteration of cell signalling. Amongst others, the new data indicate that chronic administration of a carcinogenic dose of OTA affected cell-signalling pathways resulting in a significantly reduced renal antioxidant defence and increased oxidative DNA damage. These data confirm previous hypotheses involving oxidative stress as a possible key epigenetic mechanism of OTA toxicity and carcinogenicity.

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Induction of characteristic chromosomal aberrations, particularly X-trisomy, in cultured human lymphocytes treated by ochratoxin A, A mycotoxin implicated in Balkan endemic nephropathy

Cited by 34 publications

References 13 publications

A reassessment of risk associated with dietary intake of ochratoxin A based on a lifetime exposure model

A reassessment of risk associated with dietary intake of ochratoxin A based on a lifetime exposure model

Balkan endemic nephropathy and associated urinary tract tumours: a review on aetiological causes and the potential role of mycotoxins

Ochratoxin A: Potential epigenetic mechanisms of toxicity and carcinogenicity

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