TY - JOUR
T1 - Formation of Cyclic 1,N2-Propanodeoxyguanosine Adducts in DNA upon Reaction with Acrolein or Crotonaldehyde1, 2
AU - Chung, Fung Lung
AU - Young, Ruth
AU - Hecht, Stephen S.
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1984/3/1
Y1 - 1984/3/1
N2 - Acrolein reacted with deoxyguanosine at pH 7 and 37° to give three major products, Adducts 1 to 3, which were separated by high-performance liquid chromatography. They were identified by their ultraviolet, mass, and nuclear magnetic resonance spectra, by the spectra of the corresponding guanine derivatives, and by chemical transformations. Adducts 1 and 2 were two rapidly equilibrating diastereomers of 3-(2-deoxy-β -D-erythro-pentofu-ranosyl)-5,6,7,8-tetrahydro-6-hydroxypyrimido[1,2-a]purine-10(3H)one, and Adduct 3 was 3-(2-deoxy-β -D-erythro-pentofu-ranosyl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[ 1,2-a] purine-10(3H)one. Adducts 1 and 2 were formed by Michael addition of N-1 of deoxyguanosine to C-3 of acrolein, followed by ring closure between N2 of deoxyguanosine and C-1 of acrolein. Adduct 3 was formed by ring closure in the opposite direction. Adduct 3 was analogous to the major crotonaldehyde-deoxy-guanosine adducts which were previously characterized. Adduct 3 (0.2 mmol/mol DNA-P) or the corresponding crotonaldehyde adduct (0.03 mmol/mol DNA-P) was formed when either acrolein or crotonaldehyde was allowed to react with DNA at pH 7 and 37°. These results demonstrate that cyclic 1, N2-propanodeoxy-guanosine adducts are formed by reaction of acrolein and crotonaldehyde with DNA.
AB - Acrolein reacted with deoxyguanosine at pH 7 and 37° to give three major products, Adducts 1 to 3, which were separated by high-performance liquid chromatography. They were identified by their ultraviolet, mass, and nuclear magnetic resonance spectra, by the spectra of the corresponding guanine derivatives, and by chemical transformations. Adducts 1 and 2 were two rapidly equilibrating diastereomers of 3-(2-deoxy-β -D-erythro-pentofu-ranosyl)-5,6,7,8-tetrahydro-6-hydroxypyrimido[1,2-a]purine-10(3H)one, and Adduct 3 was 3-(2-deoxy-β -D-erythro-pentofu-ranosyl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[ 1,2-a] purine-10(3H)one. Adducts 1 and 2 were formed by Michael addition of N-1 of deoxyguanosine to C-3 of acrolein, followed by ring closure between N2 of deoxyguanosine and C-1 of acrolein. Adduct 3 was formed by ring closure in the opposite direction. Adduct 3 was analogous to the major crotonaldehyde-deoxy-guanosine adducts which were previously characterized. Adduct 3 (0.2 mmol/mol DNA-P) or the corresponding crotonaldehyde adduct (0.03 mmol/mol DNA-P) was formed when either acrolein or crotonaldehyde was allowed to react with DNA at pH 7 and 37°. These results demonstrate that cyclic 1, N2-propanodeoxy-guanosine adducts are formed by reaction of acrolein and crotonaldehyde with DNA.
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M3 - Article
C2 - 6318992
AN - SCOPUS:0021319465
SN - 0008-5472
VL - 44
SP - 990
EP - 995
JO - Cancer Research
JF - Cancer Research
IS - 3
ER -