Structures and biological properties of DNA adducts derived from N-nitroso bile acid conjugates

Chemical Research in Toxicology
Yukari TotsukaKeiji Wakabayashi

Abstract

A kind of N-nitrosobile acid conjugate, N-nitrosotaurocholic acid (NO-TCA), was incubated with calf thymus DNA, and formation of an adduct was detected by the 32P-postlabeling method under nuclease P1 conditions. To examine the nucleotides containing the adduct from NO-TCA, each of 2'-deoxyribonucleotide 3'-monophosphates (3'-dAp, 3'-dGp, 3'-dCp, or 3'-Tp) was incubated with NO-TCA. The same adduct spot was detected in the reaction of NO-TCA with 3'-dCp. The structure of this adduct was determined to be 3-ethanesulfonic acid-dC by several spectrometry techniques. Moreover, bulky adducts containing bile acid moiety were also produced from the reaction of NO-TCA with 3'-dCp and 3'-dAp. From comparison with spectral data for authentic compounds, these adducts were concluded to be N4-cholyl-dC and N6-cholyl-dA. N4-Cholyl-dC and N6-cholyl-dA were also detected in calf thymus DNA treated with NO-TCA. In addition, 3-ethanesulfonic acid-dC and N4-deoxycholyl-dC were found to be produced from N-nitrosotaurodeoxycholic acid (NO-TDCA) with dC. NO-TCA and NO-TDCA induced mutations in Salmonella typhimurium TA100 but not in TA98. Mutational spectrum analysis revealed that NO-TCA induced G to A transitions predominantly. When NO-TCA (250 mg/...Continue Reading

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