TY - JOUR
T1 - Benzene and dopamine catechol quinones could initiate cancer or neurogenic disease
AU - Zahid, Muhammad
AU - Saeed, Muhammad
AU - Rogan, Eleanor G.
AU - Cavalieri, Ercole L.
N1 - Funding Information:
This research was supported by Grants P01 CA49210 from the National Cancer Institute and DAMD17-03-10229 from the Department of Defense Breast Cancer Research Program and by Prevention LLC. Core support at the Eppley Institute was provided by Grant P30 CA36727 from the National Cancer Institute .
PY - 2010/1/15
Y1 - 2010/1/15
N2 - Catechol quinones of estrogens react with DNA by 1,4-Michael addition to form depurinating N3Ade and N7Gua adducts. Loss of these adducts from DNA creates apurinic sites that can generate mutations leading to cancer initiation. We compared the reactions of the catechol quinones of the leukemogenic benzene (CAT-Q) and N-acetyldopamine (NADA-Q) with 2′-deoxyguanosine (dG) or DNA. NADA was used to prevent intramolecular cyclization of dopamine quinone. Reaction of CAT-Q or NADA-Q with dG at pH 4 afforded CAT-4-N7dG or NADA-6-N7dG, which lost deoxyribose with a half-life of 3 h to form CAT-4-N7Gua or 4 h to form NADA-6-N7Gua. When CAT-Q or NADA-Q was reacted with DNA, N3Ade adducts were formed and lost from DNA instantaneously, whereas N7Gua adducts were lost over several hours. The maximum yield of adducts in the reaction of CAT-Q or NADA-Q with DNA at pH 4 to 7 was at pH 4. When tyrosinase-activated CAT or NADA was reacted with DNA at pH 5 to 8, adduct levels were much higher (10- to 15-fold), and the highest yield was at pH 5. Reaction of catechol quinones of natural and synthetic estrogens, benzene, naphthalene, and dopamine with DNA to form depurinating adducts is a common feature that may lead to initiation of cancer or neurodegenerative disease.
AB - Catechol quinones of estrogens react with DNA by 1,4-Michael addition to form depurinating N3Ade and N7Gua adducts. Loss of these adducts from DNA creates apurinic sites that can generate mutations leading to cancer initiation. We compared the reactions of the catechol quinones of the leukemogenic benzene (CAT-Q) and N-acetyldopamine (NADA-Q) with 2′-deoxyguanosine (dG) or DNA. NADA was used to prevent intramolecular cyclization of dopamine quinone. Reaction of CAT-Q or NADA-Q with dG at pH 4 afforded CAT-4-N7dG or NADA-6-N7dG, which lost deoxyribose with a half-life of 3 h to form CAT-4-N7Gua or 4 h to form NADA-6-N7Gua. When CAT-Q or NADA-Q was reacted with DNA, N3Ade adducts were formed and lost from DNA instantaneously, whereas N7Gua adducts were lost over several hours. The maximum yield of adducts in the reaction of CAT-Q or NADA-Q with DNA at pH 4 to 7 was at pH 4. When tyrosinase-activated CAT or NADA was reacted with DNA at pH 5 to 8, adduct levels were much higher (10- to 15-fold), and the highest yield was at pH 5. Reaction of catechol quinones of natural and synthetic estrogens, benzene, naphthalene, and dopamine with DNA to form depurinating adducts is a common feature that may lead to initiation of cancer or neurodegenerative disease.
KW - 1,4-Michael addition
KW - Catechol quinones
KW - Depurinating DNA adducts
KW - Kinetics of depurination
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U2 - 10.1016/j.freeradbiomed.2009.11.002
DO - 10.1016/j.freeradbiomed.2009.11.002
M3 - Article
C2 - 19909805
AN - SCOPUS:72649092754
SN - 0891-5849
VL - 48
SP - 318
EP - 324
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 2
ER -