The endogenous
DNA adducts O(6)-carboxymethyl-deoxyguanosine (O(6)-CM-dG) and 3-ethanesulfonic
acid-
deoxycytidine (3-ESA-dC) are produced from N-nitroso
bile acid conjugates, such as
N-nitrosoglycocholic acid (NO-GCA) and
N-nitrosotaurocholic acid (NO-TCA), respectively. Formation of these
DNA adducts in vivo was here analyzed by 32P-postlabeling in the glandular stomach of rats subjected to duodenal content reflux surgery. In this model, all duodenal contents, including
bile acid conjugates, flow back from the jejunum into the gastric corpus. The levels of O(6)-CM-dG found at 4 and 8 weeks after surgery were 40.9 +/- 9.4 and 56.3 +/- 3.2 per 10(8)
nucleotides, respectively, whereas the
sham operation groups had values of 5.8 +/- 2.3 and 5.9 +/- 0.5 per 10(8)
nucleotides. Moreover, adduct spots corresponding to 3-ESA-dC were detected in both
duodenal reflux and
sham operation groups and levels in the
duodenal reflux groups were around four-fold elevated at 11.2 +/- 1.0 and 8.9 +/- 1.0 per 10(8)
nucleotides after 4 and 8 weeks, respectively. When the
duodenal reflux animals were treated with a
nitrite trapping agent,
thiazolidine- 4-carboxylic
acid (
thioproline, TPRO), the levels of O(6)-CM-dG and 3-ESA-dC were reduced to the same levels as in the
sham operation animals. These observations suggest that NO-TCA and NO-GCA are formed by nitrosation of
glycocholic acid and
taurocholic acid, respectively, and these
nitroso compounds produce
DNA adducts in the glandular stomach of rats subjected to duodenal content reflux surgery.