Effect of histamine H2-receptor antagonist therapy on the mutagenic activity of gastric juice.
There is concern at present that treatment with histamine H2-receptor antagonists might promote the development of gastric cancer by producing conditions which favour intragastric formation of N-nitroso compounds. If H2-receptor antagonist therapy causes increased intragastric levels of N-nitroso compounds, an issue not yet resolved by analytical studies, corresponding changes in the mutagenic activity of gastric juice might be anticipated. In this study mutagenic activity and pH were measured in fasting gastric aspirate from 18 peptic ulcer patients before and during the final week of therapy with ranitidine (n = 10) or cimetidine (n = 8). Mutagenic activity was assessed using Salmonella typhimurium TA98 and TA100 in a modified pre-incubation "fluctuation" test. No significant change in mutagenic activity was detected after therapy. Of 15 patients found to have significant mutagenic activity in their fasting gastric juice before treatment, 14 remained mutagenic following treatment. Mutation frequencies (sum of positive wells in duplicate 96-well microtitre plates, mean +/- SD) for TA98 and TA100 were respectively, 20 +/- 34 and 100 +/- 64 before compared with 10 +/- 6 and 102 +/- 65 after therapy (p greater than 0.05). Changes in mutagenic activity were similar in both treatment groups and unrelated to duration of therapy, changes in gastric pH or ulcer healing. In vitro, neither cimetidine in aqueous solution, nor gastric juice preincubated with cimetidine showed significant mutagenic activity. These results provide no evidence that increased intragastric levels of genotoxic chemicals, such as N-nitroso compounds, occur during H2-receptor antagonist therapy.
O'Connor
H J
HJ
Riley
S E
SE
Axon
A T
AT
Garner
R C
RC
D000328:Adult; D000368:Aged; D002927:Cimetidine / Q000627:therapeutic use*; D005260:Female; D005750:Gastric Juice / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D009152:Mutagenicity Tests; D009153:Mutagens / Q000032:analysis*; D009603:Nitroso Compounds / Q000378:metabolism; D010437:Peptic Ulcer / Q000188:drug therapy; D011899:Ranitidine / Q000627:therapeutic use*; D012486:Salmonella typhimurium / Q000187:drug effects
D009153:Mutagens; D009603:Nitroso Compounds; D002927:Cimetidine; D011899:Ranitidine