Preferential alkylation by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) of guanines with guanines as neighboring bases in DNA.

Preferential alkylation by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) of guanines with guanines as neighboring bases in DNA.
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鸟嘌呤被 1,3-双(2-氯乙基)-1-亚硝基脲 (BCNU) 优先烷基化,鸟嘌呤作为 DNA 中的相邻碱基。

DOI:
10.1016/0006-2952(88)90511-4
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发表时间:
1988
影响因子:
5.8
通讯作者:
Duarte,SP
Duarte,SP
中科院分区:
医学2区
文献类型:
--
作者:
Briscoe,WT;Duarte,SP

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The base sequence of DNA has been shown to influence the kinds and amounts of alkylation of purine bases byN-methyl-N-nitrosourea [W.T. Briscoe and L-E. Cotter,Chem. Biol. Interact.56, 321 (1985)]. In the present study, the alkylation of DNA polymers of denned sequence by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) has been investigated. The assay involved treating poly (dG)-poly(dC), poly(dG-dC)-poly(dG-dC), poly(dA-dC)-poly(dG-dT), poly(dA-dG)-poly(dC-dT), and calf thymus DNA with BCNU, followed by hydrolysis to release the modified purine bases and separation and quantitation of these by HPLC. Analysis of the results revealed that there was a 24-fold increase of 7-(β-hydroxyethyl)guanine (HOEtG) in poly(dG)-poly(dC) relative to poly(dAdG)· poly(dC-dT). There was also a 3-fold increase in HOEtG in poly(dG-dC)· poly(dG-dC), poly(dAdC)·poly(dG-dT) and calf thymus DNA relative to poly(dA-dG)· poly(dC-dT). A 2- to 4-fold increase of 7(β-aminoethyl)guanine (AmEtG) was observed in poly(dG-dC)· poly(dG-dC) relative to the other polymers tested. This study has determined that guanines in certain base sequences in polydeoxy-ribonucleotides are more susceptible to BCNU alkylation at the N-7 position than guanines in other sequences.
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