Intragastric volatile N-nitrosamines, nitrite, pH, and Helicobacter pylori during long-term treatment with omeprazole.
OBJECTIVE
This study evaluated the effect of long-term gastric acid suppressive therapy with omeprazole on intragastric levels of carcinogenic N-nitrosamines and related parameters.


METHODS
Forty-five patients on long-term omeprazole medication (mean, 35 months) and 13 healthy subjects without medication participated. Volatile N-nitrosamines were determined in gastric juice and urine. Intragastric pH, nitrite, nitrate, and H. pylori status were determined. DNA isolated from gastric biopsy specimens was analyzed for precarcinogenic alkyl-DNA adducts.


RESULTS
The intragastric pH in patients was significantly higher compared with controls (P = 0.0001). Gastric nitrite levels in patients were nonsignificantly higher. There was no difference in total levels of intragastric volatile N-nitrosamines between patients and controls, however, urinary N-nitrosodimethylamine excretion was higher in patients (P = 0.001). On omeprazole, Helicobacter pylori-positive vs. -negative patients had a nonsignificantly higher intragastric nitrite level and higher urinary N-nitrosodimethylamine excretion. No alkyl-DNA adducts could be detected in gastric epithelium.


CONCLUSIONS
Increased intragastric pH caused by long-term treatment with omeprazole does not result in increased intragastric levels of nitrite and volatile N-nitrosamines. The significantly higher urinary N-nitrosamine excretion implies the risk of increased endogenous formation of N-nitrosamines during long-term omeprazole treatment. This risk may be higher in H. pylori-positive patients.
Vermeer
I T
IT
Department of Health Risk Analysis and Toxicology, Maastricht University, Maastricht, The Netherlands. Ingrid.Vermeer@numico-research.nl
Engels
L G
LG
Pachen
D M
DM
Dallinga
J W
JW
Kleinjans
J C
JC
van Maanen
J M
JM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000897:Anti-Ulcer Agents / Q000009:adverse effects*; D001706:Biopsy; D005260:Female; D005750:Gastric Juice / Q000737:chemistry / Q000382:microbiology; D016481:Helicobacter Infections / Q000453:epidemiology / Q000473:pathology*; D016480:Helicobacter pylori / Q000302:isolation & purification*; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009573:Nitrites / Q000032:analysis*; D009602:Nitrosamines / Q000032:analysis*; D009853:Omeprazole / Q000009:adverse effects*; D054328:Proton Pump Inhibitors; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000473:pathology
D000897:Anti-Ulcer Agents; D009573:Nitrites; D009602:Nitrosamines; D054328:Proton Pump Inhibitors; D009853:Omeprazole