Selective inhibition of the BPDE-I-induced modification of the replicating DNA of S-phase cells, by benzamide and 3-aminobenzamide.
Selective inhibition of the BPDE-I-induced modification of the replicating DNA of S-phase cells, by benzamide and 3-aminobenzamide.
复制标题
苯甲酰胺和 3-氨基苯甲酰胺选择性抑制 BPDE-I 诱导的 S 期细胞复制 DNA 的修饰。
DOI：
10.1093/carcin/13.3.489
复制
发表时间：
1992
期刊：
影响因子：
4.7
通讯作者：
Milo,GE
中科院分区：
文献类型：
--
作者：
Kurian,P;Kumari,HL;Milo,GE
Treatment of human skin fibroblasts in early S-phase with (±)7β,8α-dihydroxy-9α, 10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE-I) results in more extensive modification of early replicating DNA than parental DNA. We have investigated the effects of benzamide (BZ) and 3-aminobenzamide (3-ABZ), inhibitors of transformation, on the modification of parental and replicating DNA of cells in early S-phase by BPDE-I. Synchronized cells were exposed to 5-bromodeoxyuridine at S-phase entry and treated 3 h later with 0.114 μM BPDE-I for 30 min. The cells at the time of treatment represent a radiolabeling index of 40±5% of the total number of cells. The replicated DNA was isolated from the non-replicated parental DNA on a CsCI gradient. A32P-postlabeling procedure was used to quantitate the carcinogen—DNA adducts. The level of modification per nucleotide residue of the early replicated DNA was 1.6–2.2 times higher compared to the level of modification of the parental DNA. Addition of BZ inhibited the BPDE-I modification of the replicated DNA by 27–53%. There was no significant effect on the parental DNA modification. The major adduct that was quantitatively suppressed in the early replicated DNA was BPDE-I-trans-N2-dG. The addition of 3-ABZ also inhibited the modification of the dG by ∼50% without significantly inhibiting the BPDE-I-dG adducts in the parental DNA. The data suggest that BZ and 3-ABZ inhibit the modification of specific sites in the replicating DNA leading to inhibition of transformation.
