Evaluation of omeprazole genotoxicity in a battery of in vitro and in vivo assays
| Autor: | Giulia Brambilla Campart, Francesca Mattioli, Giovanni Brambilla, Antonietta Martelli, Giovanna Bergamaschi, Eugenio Mereto, Daniela Sini |
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| Rok vydání: | 1998 |
| Předmět: |
Adult
Male DNA Repair Colon Pharmacology Biology Toxicology medicine.disease_cause Rats Sprague-Dawley chemistry.chemical_compound Oral administration In vivo medicine Animals Humans Lymphocytes Cells Cultured Omeprazole Aged Micronucleus Tests Mutagenicity Tests Azoxymethane Anti-Ulcer Agents Rats Liver chemistry Biochemistry Micronucleus test Toxicity Female Genotoxicity medicine.drug Aberrant crypt foci |
| Zdroj: | Toxicology. 130:29-41 |
| ISSN: | 0300-483X |
| Popis: | Omeprazole, a proton pump inhibitor of wide use in the treatment of gastric acid-related disorders, was evaluated for its genotoxic effects in both rat and human cultured cells and in the intact rat. DNA repair synthesis, as revealed by autoradiography, was detected in primary cultures of metabollically competent rat hepatocytes exposed to concentrations ranging from 10 to 100 mg/l, but the responses cannot be considered as clearly positive. Under the same experimental conditions any significant evidence of DNA repair was absent in primary hepatocytes from two human donors. At the same concentrations a modest but dose-related increase of micronucleated cells, that reached the level of statistical significance at 33 mg/l, was present in primary rat hepatocytes and in one of two human donors. In human lymphocytes exposed to subtoxic concentrations ranging from 0.78 to 12.5 mg/l a reproducible concentration dependent clastogenic effect was absent. In partially hepatectomized female rats treated with a single p.o. dose of 1000 mg/kg, the frequency of micronucleated cells was 5.2-fold higher than in controls in the liver, but only 2.0-fold higher in polychromatic erythrocytes of the bone marrow. In rats of the same sex given azoxymethane as initiator of colon carcinogenesis the oral administration for 8 successive weeks of 10 mg/kg omeprazole on alternate days increased the response to azoxymethane, as indicated by the occurrence in colon mucosa of a modest but statistically significant increase in both the average number and size of aberrant crypt foci. Taken as a whole, our results suggest that omeprazole behaves as a weak genotoxic agent for the rat liver. Reliable information about the potential genotoxic risk to humans requires further studies on primary cells from a wide number of donors. |
| Databáze: | OpenAIRE |
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