Lack of evidence of omeprazole genotoxicity in Sprague-Dawley rats

Omeprazole is a proton pump inhibitor of increasingly wide usein the treatment of peptic ulcers. Although omeprazole has beensubjected to an extensive range of genotoxicity tests, whichhave all been concluded as negative, the ability of this compoundto interact with DNA and elicit unscheduled DNA synthesis inthe rat gastric mucosa has been the subject of debate. Therefore,we have examined omeprazole using other genotoxicity end-points.In female Sprague-Dawley rats, the administration by the oralroute of 100 mg/kg, either as neutral (pH 7.0) suspension oras suspension acidified to pH 1.5, which favours its transformationinto the active form of sulphenamide, did not induce DNA fragmentationin gastric mucosa and liver, as detected by the alkaline elutiontechnique. In the same experimental conditions, a frequencyof total nuclear anomalies (micronuclei, pyknosis and karyorrhexis)that was significantly higher than in controls was detectedwith both types of suspension in forestomach and descendingcolon mucosa. However, in both tissues this higher frequencyof nuclear anomalies was mostly due to pyknosis and karyorrhexis,which may be the outcome of a non-genotoxic effect, whereasthere was no significant increase in the number of micronucleatedcells, and this suggests the absence of clastogenic activity.Finally, in rats initiated with N-nitrosodiethylamine, the oraladministration of 100 mg/kg omeprazole for 14 successive daysproduced a modest but statistically significant increase ofliver -glutamyltranspeptidase positive foci, which is consistentwith a potential promoting activity. Taken as a whole and comparedwith previous findings our results add further doubts aboutthe undiscriminated capability of omeprazole to behave as agenotoxic carcinogen and provide evidence that the occurrenceof a genotoxic effect, if it actually takes place, is limitedto some strains of rats. ¹To whom correspondence should be addressed