An in vivo unscheduled DNA synthesis (UDS) assay in the rat gastric mucosa: preliminary development.
A new in vivo unscheduled DNA synthesis (UDS) assay is described for the detection of genotoxic damage in the rat stomach. In this assay advantage is taken of the morphology of the gastric mucosa to enable the selective isolation, and subsequent measurement of UDS, in non-S-phase cells. The absence of replicating cells allows UDS to be measured by scintillation counting without having to use hydroxyurea. Control background responses are given, these were low and acceptably stable. The sensitivity of the assay was tested using 1-methyl-3-nitro-1-nitrosoguanidine which was found positive at doses as low as 12.5 mg/kg. The selectivity of the assay for genotoxins was tested using indomethacin, a nongenotoxic, gastric irritant. This compound was negative at dose levels and exposure times known to produce gastric lesions. Two forestomach-specific carcinogens, aristolochic acid and epichlorhydrin, were also investigated. Aristolochic acid was, surprisingly, uniformly negative. Further work on this compound is obviously required especially in the light of the strong positive response produced by epichlorhydrin. These data would suggest that this assay would be a useful complement to the current in vivo short-term test battery and a helpful research tool for investigating DNA repair in stomach tissue.
Burlinson
B
B
Glaxo Group Research Ltd, Ware, Herts, UK.
D000818:Animals; D034341:Aristolochic Acids; D015197:Carcinogenicity Tests / Q000379:methods; D002273:Carcinogens / Q000494:pharmacology*; D002728:Chlorohydrins / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects / Q000302:isolation & purification; D004261:DNA Replication / Q000187:drug effects; D004811:Epichlorohydrin / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology*; D010616:Phenanthrenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D034341:Aristolochic Acids; D002273:Carcinogens; D002728:Chlorohydrins; D010616:Phenanthrenes; D004811:Epichlorohydrin; D008769:Methylnitronitrosoguanidine; D004247:DNA; C000228:aristolochic acid I; D007213:Indomethacin