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E Creppy

Publications and source records attributed to E Creppy.

5 recordsLinked to original sources

Cytotoxicity, inhibition of DNA and protein syntheses and oxidative damage in cultured cells exposed to zearalenone.

Mycotoxins are toxic metabolites of various fungi commonly found in feed and foodstuff and can cause very serious health problems in animals as well as in humans. Zearalenone (ZEN), a mycotoxin produced by various Fusarium species has several adverse effects. Indeed, ZEN has strong estrogenic activity associated with hyperestrogenism and several physiological alterations of the reproductive tract. Moreover, ZEN was shown to be hepatotoxic, haematotoxic, immunotoxic and genotoxic. The exact mechanism of ZEN toxicity is not completely established. The observed strong estrogenic effect of ZEN resulting from its competition with 17beta-estradiol in the binding to estrogen receptors is generally considered to underline most toxic effects of ZEN, but estrogenic activity alone cannot explain the diverse and apparent adverse effects. The objective of the present study was to determine the involvement of other possible mechanisms in ZEN induced toxicity. Cytotoxicity, cell cycle perturbation, inhibition of protein and DNA synthesis as well as the presumed later marker of oxidative stress, malondialdehyde, were monitored in Vero and Caco-2 cells exposed to ZEN. Our results showed that ZEN reduces cell viability correlated to cell cycle perturbation, inhibits protein and DNA syntheses and increases MDA formation in both cell lines in concentration-dependant manner. We assumed that cytotoxicity and oxidative damage are additional mechanisms of ZEN mediated toxicity.

Animals↗

Oxythiamine and dehydroepiandrosterone induce a G1 phase cycle arrest in Ehrlich's tumor cells through inhibition of the pentose cycle.

Transketolase (TK) reactions play a crucial role in tumor cell nucleic acid ribose synthesis utilizing glucose carbons, yet, current cancer treatments do not target this central pathway. Experimentally, a dramatic decrease in tumor cell proliferation after the administration of the TK inhibitor oxythiamine (OT) was observed in several in vitro and in vivo tumor models. Here, we demonstrate that pentose cycle (PC) inhibitors, OT and dehydroepiandrosterone (DHEA), efficiently regulate the cell cycle and tumor proliferation processes. Increasing doses of OT or DHEA were administered by daily intraperitoneal injections to Ehrlich's ascites tumor hosting mice for 4 days. The tumor cell number and their cycle phase distribution profile were determined by DNA flow histograms. Tumors showed a dose dependent increase in their G0-G1 cell populations after both OT and DHEA treatment and a simultaneous decrease in cells advancing to the S and G2-M cell cycle phases. This effect of PC inhibitors was significant, OT was more effective than DHEA, both drugs acted synergistically in combination and no signs of direct cell or host toxicity were observed. Direct inhibition of PC reactions causes a G1 cell cycle arrest similar to that of 2-deoxyglucose treatment. However, no interference with cell energy production and cell toxicity is observed. PC inhibitors, specifically ones targeting TK, introduce a new target site for the development of future cancer therapies to inhibit glucose utilizing pathways selectively for nucleic acid production.

Animals↗

[Preventive action of phenylalanine on acute intoxication of ochratoxin-A].

Ochratoxin-A, a mycotoxin causing kidney and liver damage, inhibits protein synthesis by competition with phenylalanine in the phenylalanyl-tRNA synthetase catalysed reaction. A dose of 0,8 mg ochratoxine per Mouse is 100% lethal within 24 hrs, when injected intraperitoneally. When phenylalanine is injected simultaneously with ochratoxine-A, the survival of the animals was 100% for 1 mg of phenylalanine per Mouse. Ten times higher doses of phenylalanine are necessary to obtain a 85% survival if the amino acid is injected 30 min. after the mycotoxin. Phenylalanine gives a very low protection if injected 1 hr or more ochratoxine-A.

Animals↗