Detection of endogenous DNA adducts, O-carboxymethyl-2'-deoxyguanosine and 3-ethanesulfonic acid-2'-deoxycytidine, in the rat stomach after duodenal reflux.
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.
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045;
Masaru
M
Terasaki
Yukari
Y
Totsuka
Koichi
K
Nishimura
Ken-Ichi
K
Mukaisho
Kuan-Hao
KH
Chen
Takanori
T
Hattori
Takeji
T
Takamura-Enya
Takashi
T
Sugimura
Keiji
K
Wakabayashi
D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry*; D018736:DNA Adducts / Q000032:analysis* / Q000737:chemistry; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000032:analysis; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D004383:Duodenogastric Reflux / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D013270:Stomach / Q000737:chemistry*; D013451:Sulfonic Acids / Q000032:analysis
C533181:3-ethanesulfonic acid 2'-deoxycytidine; D001647:Bile Acids and Salts; D018736:DNA Adducts; C107252:O(6)-(carboxymethyl)-2'-deoxyguanosine; D013451:Sulfonic Acids; D003841:Deoxycytidine; D003849:Deoxyguanosine