Cell isolation and genotoxicity assessment in gastric mucosa.
It has been claimed that in vitro digestion of in vivo DNA-labeled gastric mucosa is suitable for evaluation of genotoxic effects of drugs or chemicals. This method was then used to show that omeprazole (a novel antiulcer drug) was potentially genotoxic. In this study we have examined the method used and the interaction of omeprazole and its derivatives with purified DNA. The method was shown to enrich for dividing cells (6.92 +/- 0.693%, N = 43, 2-hr labeling) in the digest from the intact tissue and was therefore unsuitable for estimating unscheduled DNA synthesis in the gastric mucosa induced by chemicals or drugs including omeprazole. It was further shown that neither omeprazole or its acid-activated product, a cationic sulfenamide, were able to react with isolated purified DNA from either a prokaryote (E. coli) or a eukaryote (salmon sperm). Hence any conclusions using this method attributing acute genotoxic effects to any chemical are based on unrecognized artifacts of the technique and are unsound. In addition, these results negate the suggestion that omeprazole or its gastric metabolites are genotoxic.
Center for Ulcer Research and Education, VA West Los Angeles Medical Center.
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Scott
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Reuben
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Zampighi
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Sachs
D000818:Animals; D001973:Bromodeoxyuridine; D002469:Cell Separation / Q000379:methods; D004247:DNA / Q000187:drug effects*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D009337:Necturus; D009853:Omeprazole / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D004247:DNA; D001973:Bromodeoxyuridine; D009853:Omeprazole