DNA synthesis and genotoxicity

Digestion
N A Wright

Abstract

In a recent report, Burlinson et al. [Carcinogenesis 1989;10:1425-1428] published the results of an experiment which they claim shows that omeprazole induces unscheduled DNA synthesis (UDS) in rat gastric mucosa (i.e. DNA repair). The Burlinson method measures the incorporation of tritiated thymidine into cells undergoing DNA synthesis. Rat stomachs are exposed to test substances for 14 h in vivo, tritiated thymidine is injected and the animals killed 1 h later. Superficial cells are isolated by a selective digestion with pronase for 45 min, and the level of UDS in the cell isolate is measured by scintillation counting. However, differentiation of UDS in the gastric mucosa from the scheduled DNA synthesis which accompanies cell division is technically difficult. Scheduled DNA synthesis is maximal around the isthmus neck junction of the gastric glands, but is detectable (by labelling with tritiated thymidine) up to five cell positions from the surface. Any method which relies on selective separation of non-dividing surface cells to identify UDS requires stringent controls to exclude contamination with deeper dividing cells. This is particularly important in situations where there is a stimulus to cell proliferation, as occurs wh...Continue Reading

Citations

Mar 1, 1995·Pharmacology & Therapeutics·R E PowersI M Modlin
Feb 27, 2013·Applied Physiology, Nutrition, and Metabolism = Physiologie Appliquée, Nutrition Et Métabolisme·Shubhra Pande, Krishnapura Srinivasan
Mar 23, 2011·Evidence-based Complementary and Alternative Medicine : ECAM·R S DeodaS S Bhujbal
Dec 1, 1991·Alimentary Pharmacology & Therapeutics·K G Wormsley

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