Zearalenone induces chromosome aberrations in mouse bone marrow: preventive effect of 17β-estradiol, progesterone and Vitamin E

The cytogenetic effect of zearalenone (ZEN), a non-steroidal estrogenic mycotoxin, was evaluated in vivo, in mouse bone marrow cells, by assessing the percentage of cells bearing different chromosome aberrations. The studies included different conditions for animal treatment, as follows: (1) single intraperitoneal (ip) injection, (2) repeated ip injections, (3) pre-treatment for 24 h with Vitamin E (Vit E), and (4) pre-treatment for 4 h with 17β-estradiol (17β-Est) or progesterone (Prog). ZEN induced different types of chromosome aberrations, which was concentration-dependent (2–20 mg/kg bw). These doses corresponded to 0.4–4% of the LD₅₀ in the mouse. Interestingly, when the dose of ZEN (40 mg/kg) was fractionated into four equivalent doses (4 × 10 mg/kg bw), into three doses (15 + 10 + 15 mg/kg bw), or into two equivalent doses (2 × 20 mg/kg bw), given every 24 h, the percentage of chromosome aberrations increased significantly. This finding suggests that ZEN proceeds by reversible binding on receptors that could become saturated, and that it damages the chromosomes in a ‘hit and go’ manner. Furthermore, pre-treatment of animals with 17β-estradiol or progesterone significantly decreased the percentage of chromosome aberrations, suggesting that (i) these hormones bind to the same cytoplasmic receptors transported into the nucleus to elicit DNA damage, (ii) they may play a role in preventing chromosome aberrations induced by ZEN. Similarly, Vit E prevented these chromosome aberrations indicating that Vit E, previously reported to prevent most of the toxic effects induced by ZEN, may also bind to the same receptors.     

New Structural Motifs for Hammerhead Ribozymes. Catalytic Activity of Abasic Nucleotide Substituted Ribozymes

Abstract

The synthesis of 1-deoxy-D-ribofuranose-3-(2-cyanoethyl N,N-diisopropylphosphoramidite) (6) from D-ribose and its incorporation into a hammerhead ribozyme is described.     

Template-directed primer extension catalyzed by the Tetrahymena ribozyme.

The Tetrahymena ribozyme has been shown to catalyze an RNA polymerase-like reaction in which an RNA primer is extended by the sequential addition of pN nucleotides derived from GpN dinucleotides, where N = A, C, or U. Here, we show that this reaction is influenced by the presence of a template; bases that can form Watson-Crick base pairs with a template add as much as 25-fold more efficiently than mismatched bases. A mutant enzyme with an altered guanosine binding site can catalyze template-directed primer extension with all four bases when supplied with dinucleotides of the form 2-aminopurine-pN.     

Synthesis of 6-Aza- & 6-Methyl-pyrimidine Ribonucleoside Phosphoramidites and Their Incorporation in Hammerhead Ribozymes

Abstract

The synthesis of phosphoramidites of 6-modified pyrimidine ribonucleosides and their incorporation into hammerhead ribozymes and influence on nuclease stability and catalytic activity is described.     

Crocin Prevents Patulin‐Induced Acute Toxicity in Cardiac Tissues via the Regulation of Oxidative Damage and Apoptosis

Patulin (PAT) is a mycotoxin produced by several species of the genera of Penicillium, Aspergillus, and Byssochlamys principally by Penicillium expansum. This mycotoxin is suspected to affect several organs including kidney and liver. However, its toxic effect on heart remains unknown. The present study investigated for the first time the cardiotoxic effect of PAT in mice. We demonstrated that PAT increased creatinin phosphokinase (CPK) level, induced lipoperoxydation and protein oxidation, and triggered the antioxidant enzymes such as superoxide dismutase and catalase activities. We also demonstrated that acute administration of PAT triggers apoptosis via P53 overexpression and caspase 3 activation. We further investigated the antioxidant efficiency of crocin (CRO), a carotenoid pigment, against PAT‐induced cardiotoxicity. We found that pretreatment with CRO prevents cardiac impairment by reducing CPK levels, restoring the redox statute and suppressing apoptosis. Collectively, our data provide new preventive effect of CRO toward PAT‐induced cardiotoxicity in mice.     

Aptness of Beauveria bassiana and enhanced diatomaceous earth (DEBBM) for control of Rhyzopertha dominica F.

A diatomaceous earth formulation enhanced with bitterbarkomycin (DEBBM) combined with Beauveria bassiana (Balsamo) Vuillemin was evaluated against lesser grain borer Rhyzopertha dominica F. (Coleoptera: Bostrychidae) under laboratory conditions. DEBBM was applied at the rates of 15 and 30 ppm alone as well as in combination with 6.69 × 10⁶, 6.69 × 10⁸ and 6.69 × 10¹⁰ conidia/kg of wheat. Mortality of treated adults was recorded after 5, 10 and 15 days of exposure. Bioassays were carried out at 20, 25 and 30°C with 55 and 75% relative humidity. The emergence of progeny was also assessed 60 days post exposure. The combined use of DEBBM and B. bassiana considerably increased adult mortality especially at increasing temperatures and longer exposure intervals compared with DEBBM and B. bassiana alone. Progeny production was less in wheat treated with high dose rates of DEBBM +B. bassiana. The per cent mycosis in the cadavers was maximum where B. bassiana was applied at low dose rates. The results of the present study indicated that a combination of DEBBM and B. bassiana may provide effective control of R. dominica.